Int J Cell Biol. 2016; 2016: 6940283.

Department of Biological Sciences, Indian Institute of Science Education and Research (IISER), Bhopal, Madhya Pradesh 462066, India

Department of Biological Sciences, Indian Institute of Science Education and Research (IISER), Bhopal, Madhya Pradesh 462066, India

Academic Editor: Paul J. Higgins

Received 2016 Mar 13; Accepted 2016 Jun 5.

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of tissues or organs for the patient suffering from severe injuries or chronic disease. The spectacular progress in the field of stem cell research has laid the foundation for cell based therapies of disease which cannot be cured by conventional medicines. The indefinite self-renewal and potential to differentiate into other types of cells represent stem cells as frontiers of regenerative medicine. The transdifferentiating potential of stem cells varies with source and according to that regenerative applications also change. Advancements in gene editing and tissue engineering technology have endorsed the ex vivo remodelling of stem cells grown into 3D organoids and tissue structures for personalized applications. This review outlines the most recent advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells regenerative application in wildlife conservation.

Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of specific tissue and/or organ of the patients suffering with severe injuries or chronic disease conditions, in the state where bodies own regenerative responses do not suffice [1]. In the present scenario donated tissues and organs cannot meet the transplantation demands of aged and diseased populations that have driven the thrust for search for the alternatives. Stem cells are endorsed with indefinite cell division potential, can transdifferentiate into other types of cells, and have emerged as frontline regenerative medicine source in recent time, for reparation of tissues and organs anomalies occurring due to congenital defects, disease, and age associated effects [1]. Stem cells pave foundation for all tissue and organ system of the body and mediates diverse role in disease progression, development, and tissue repair processes in host. On the basis of transdifferentiation potential, stem cells are of four types, that is, (1) unipotent, (2) multipotent, (3) pluripotent, and (4) totipotent [2]. Zygote, the only totipotent stem cell in human body, can give rise to whole organism through the process of transdifferentiation, while cells from inner cells mass (ICM) of embryo are pluripotent in their nature and can differentiate into cells representing three germ layers but do not differentiate into cells of extraembryonic tissue [2]. Stemness and transdifferentiation potential of the embryonic, extraembryonic, fetal, or adult stem cells depend on functional status of pluripotency factors like OCT4, cMYC, KLF44, NANOG, SOX2, and so forth [35]. Ectopic expression or functional restoration of endogenous pluripotency factors epigenetically transforms terminally differentiated cells into ESCs-like cells [3], known as induced pluripotent stem cells (iPSCs) [3, 4]. On the basis of regenerative applications, stem cells can be categorized as embryonic stem cells (ESCs), tissue specific progenitor stem cells (TSPSCs), mesenchymal stem cells (MSCs), umbilical cord stem cells (UCSCs), bone marrow stem cells (BMSCs), and iPSCs (; ). The transplantation of stem cells can be autologous, allogenic, and syngeneic for induction of tissue regeneration and immunolysis of pathogen or malignant cells. For avoiding the consequences of host-versus-graft rejections, tissue typing of human leucocyte antigens (HLA) for tissue and organ transplant as well as use of immune suppressant is recommended [6]. Stem cells express major histocompatibility complex (MHC) receptor in low and secret chemokine that recruitment of endothelial and immune cells is enabling tissue tolerance at graft site [6]. The current stem cell regenerative medicine approaches are founded onto tissue engineering technologies that combine the principles of cell transplantation, material science, and microengineering for development of organoid; those can be used for physiological restoration of damaged tissue and organs. The tissue engineering technology generates nascent tissue on biodegradable 3D-scaffolds [7, 8]. The ideal scaffolds support cell adhesion and ingrowths, mimic mechanics of target tissue, support angiogenesis and neovascularisation for appropriate tissue perfusion, and, being nonimmunogenic to host, do not require systemic immune suppressant [9]. Stem cells number in tissue transplant impacts upon regenerative outcome [10]; in that case prior ex vivo expansion of transplantable stem cells is required [11]. For successful regenerative outcomes, transplanted stem cells must survive, proliferate, and differentiate in site specific manner and integrate into host circulatory system [12]. This review provides framework of most recent (; Figures ) advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells as the tool of regenerative applications in wildlife conservation.

Promises of stem cells in regenerative medicine: the six classes of stem cells, that is, embryonic stem cells (ESCs), tissue specific progenitor stem cells (TSPSCs), mesenchymal stem cells (MSCs), umbilical cord stem cells (UCSCs), bone marrow stem cells (BMSCs), and induced pluripotent stem cells (iPSCs), have many promises in regenerative medicine and disease therapeutics.

ESCs in regenerative medicine: ESCs, sourced from ICM of gastrula, have tremendous promises in regenerative medicine. These cells can differentiate into more than 200 types of cells representing three germ layers. With defined culture conditions, ESCs can be transformed into hepatocytes, retinal ganglion cells, chondrocytes, pancreatic progenitor cells, cone cells, cardiomyocytes, pacemaker cells, eggs, and sperms which can be used in regeneration of tissue and treatment of disease in tissue specific manner.

TSPSCs in regenerative medicine: tissue specific stem and progenitor cells have potential to differentiate into other cells of the tissue. Characteristically inner ear stem cells can be transformed into auditory hair cells, skin progenitors into vascular smooth muscle cells, mesoangioblasts into tibialis anterior muscles, and dental pulp stem cells into serotonin cells. The 3D-culture of TSPSCs in complex biomaterial gives rise to tissue organoids, such as pancreatic organoid from pancreatic progenitor, intestinal tissue organoids from intestinal progenitor cells, and fallopian tube organoids from fallopian tube epithelial cells. Transplantation of TSPSCs regenerates targets tissue such as regeneration of tibialis muscles from mesoangioblasts, cardiac tissue from AdSCs, and corneal tissue from limbal stem cells. Cell growth and transformation factors secreted by TSPSCs can change cells fate to become other types of cell, such that SSCs coculture with skin, prostate, and intestine mesenchyme transforms these cells from MSCs into epithelial cells fate.

MSCs in regenerative medicine: mesenchymal stem cells are CD73+, CD90+, CD105+, CD34, CD45, CD11b, CD14, CD19, and CD79a cells, also known as stromal cells. These bodily MSCs represented here do not account for MSCs of bone marrow and umbilical cord. Upon transplantation and transdifferentiation these bodily MSCs regenerate into cartilage, bones, and muscles tissue. Heart scar formed after heart attack and liver cirrhosis can be treated from MSCs. ECM coating provides the niche environment for MSCs to regenerate into hair follicle, stimulating hair growth.

UCSCs in regenerative medicine: umbilical cord, the readily available source of stem cells, has emerged as futuristic source for personalized stem cell therapy. Transplantation of UCSCs to Krabbe's disease patients regenerates myelin tissue and recovers neuroblastoma patients through restoring tissue homeostasis. The UCSCs organoids are readily available tissue source for treatment of neurodegenerative disease. Peritoneal fibrosis caused by long term dialysis, tendon tissue degeneration, and defective hyaline cartilage can be regenerated by UCSCs. Intravenous injection of UCSCs enables treatment of diabetes, spinal myelitis, systemic lupus erythematosus, Hodgkin's lymphoma, and congenital neuropathies. Cord blood stem cells banking avails long lasting source of stem cells for personalized therapy and regenerative medicine.

BMSCs in regenerative medicine: bone marrow, the soft sponge bone tissue that consisted of stromal, hematopoietic, and mesenchymal and progenitor stem cells, is responsible for blood formation. Even halo-HLA matched BMSCs can cure from disease and regenerate tissue. BMSCs can regenerate craniofacial tissue, brain tissue, diaphragm tissue, and liver tissue and restore erectile function and transdifferentiation monocytes. These multipotent stem cells can cure host from cancer and infection of HIV and HCV.

iPSCs in regenerative medicine: using the edge of iPSCs technology, skin fibroblasts and other adult tissues derived, terminally differentiated cells can be transformed into ESCs-like cells. It is possible that adult cells can be transformed into cells of distinct lineages bypassing the phase of pluripotency. The tissue specific defined culture can transform skin cells to become trophoblast, heart valve cells, photoreceptor cells, immune cells, melanocytes, and so forth. ECM complexation with iPSCs enables generation of tissue organoids for lung, kidney, brain, and other organs of the body. Similar to ESCs, iPSCs also can be transformed into cells representing three germ layers such as pacemaker cells and serotonin cells.

Stem cells in wildlife conservation: tissue biopsies obtained from dead and live wild animals can be either cryopreserved or transdifferentiated to other types of cells, through culture in defined culture medium or in vivo maturation. Stem cells and adult tissue derived iPSCs have great potential of regenerative medicine and disease therapeutics. Gonadal tissue procured from dead wild animals can be matured, ex vivo and in vivo for generation of sperm and egg, which can be used for assistive reproductive technology oriented captive breeding of wild animals or even for resurrection of wildlife.

Application of stem cells in regenerative medicine: stem cells (ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs) have diverse applications in tissue regeneration and disease therapeutics.

For the first time in 1998, Thomson isolated human ESCs (hESCs) [13]. ESCs are pluripotent in their nature and can give rise to more than 200 types of cells and promises for the treatment of any kinds of disease [13]. The pluripotency fate of ESCs is governed by functional dynamics of transcription factors OCT4, SOX2, NANOG, and so forth, which are termed as pluripotency factors. The two alleles of the OCT4 are held apart in pluripotency state in ESCs; phase through homologues pairing during embryogenesis and transdifferentiation processes [14] has been considered as critical regulatory switch for lineage commitment of ESCs. The diverse lineage commitment potential represents ESCs as ideal model for regenerative therapeutics of disease and tissue anomalies. This section of review on ESCs discusses transplantation and transdifferentiation of ESCs into retinal ganglion, hepatocytes, cardiomyocytes, pancreatic progenitors, chondrocytes, cones, egg sperm, and pacemaker cells (; ). Infection, cancer treatment, and accidents can cause spinal cord injuries (SCIs). The transplantation of hESCs to paraplegic or quadriplegic SCI patients improves body control, balance, sensation, and limbal movements [15], where transplanted stem cells do homing to injury sites. By birth, humans have fixed numbers of cone cells; degeneration of retinal pigment epithelium (RPE) of macula in central retina causes age-related macular degeneration (ARMD). The genomic incorporation of COCO gene (expressed during embryogenesis) in the developing embryo leads lineage commitment of ESCs into cone cells, through suppression of TGF, BMP, and Wnt signalling pathways. Transplantation of these cone cells to eye recovers individual from ARMD phenomenon, where transplanted cone cells migrate and form sheet-like structure in host retina [16]. However, establishment of missing neuronal connection of retinal ganglion cells (RGCs), cones, and PRE is the most challenging aspect of ARMD therapeutics. Recently, Donald Z Jacks group at John Hopkins University School of Medicine has generated RGCs from CRISPER-Cas9-m-Cherry reporter ESCs [17]. During ESCs transdifferentiation process, CRIPER-Cas9 directs the knock-in of m-Cherry reporter into 3UTR of BRN3B gene, which is specifically expressed in RGCs and can be used for purification of generated RGCs from other cells [17]. Furthermore, incorporation of forskolin in transdifferentiation regime boosts generation of RGCs. Coaxing of these RGCs into biomaterial scaffolds directs axonal differentiation of RGCs. Further modification in RGCs generation regime and composition of biomaterial scaffolds might enable restoration of vision for ARMD and glaucoma patients [17]. Globally, especially in India, cardiovascular problems are a more common cause of human death, where biomedical therapeutics require immediate restoration of heart functions for the very survival of the patient. Regeneration of cardiac tissue can be achieved by transplantation of cardiomyocytes, ESCs-derived cardiovascular progenitors, and bone marrow derived mononuclear cells (BMDMNCs); however healing by cardiomyocytes and progenitor cells is superior to BMDMNCs but mature cardiomyocytes have higher tissue healing potential, suppress heart arrhythmias, couple electromagnetically into hearts functions, and provide mechanical and electrical repair without any associated tumorigenic effects [18, 19]. Like CM differentiation, ESCs derived liver stem cells can be transformed into Cytp450-hepatocytes, mediating chemical modification and catabolism of toxic xenobiotic drugs [20]. Even today, availability and variability of functional hepatocytes are a major a challenge for testing drug toxicity [20]. Stimulation of ESCs and ex vivo VitK12 and lithocholic acid (a by-product of intestinal flora regulating drug metabolism during infancy) activates pregnane X receptor (PXR), CYP3A4, and CYP2C9, which leads to differentiation of ESCs into hepatocytes; those are functionally similar to primary hepatocytes, for their ability to produce albumin and apolipoprotein B100 [20]. These hepatocytes are excellent source for the endpoint screening of drugs for accurate prediction of clinical outcomes [20]. Generation of hepatic cells from ESCs can be achieved in multiple ways, as serum-free differentiation [21], chemical approaches [20, 22], and genetic transformation [23, 24]. These ESCs-derived hepatocytes are long lasting source for treatment of liver injuries and high throughput screening of drugs [20, 23, 24]. Transplantation of the inert biomaterial encapsulated hESCs-derived pancreatic progenitors (CD24+, CD49+, and CD133+) differentiates into -cells, minimizing high fat diet induced glycemic and obesity effects in mice [25] (). Addition of antidiabetic drugs into transdifferentiation regime can boost ESCs conservation into -cells [25], which theoretically can cure T2DM permanently [25]. ESCs can be differentiated directly into insulin secreting -cells (marked with GLUT2, INS1, GCK, and PDX1) which can be achieved through PDX1 mediated epigenetic reprogramming [26]. Globally, osteoarthritis affects millions of people and occurs when cartilage at joints wears away, causing stiffness of the joints. The available therapeutics for arthritis relieve symptoms but do not initiate reverse generation of cartilage. For young individuals and athletes replacement of joints is not feasible like old populations; in that case transplantation of stem cells represents an alternative for healing cartilage injuries [27]. Chondrocytes, the cartilage forming cells derived from hESC, embedded in fibrin gel effectively heal defective cartilage within 12 weeks, when transplanted to focal cartilage defects of knee joints in mice without any negative effect [27]. Transplanted chondrocytes form cell aggregates, positive for SOX9 and collagen II, and defined chondrocytes are active for more than 12wks at transplantation site, advocating clinical suitability of chondrocytes for treatment of cartilage lesions [27]. The integrity of ESCs to integrate and differentiate into electrophysiologically active cells provides a means for natural regulation of heart rhythm as biological pacemaker. Coaxing of ESCs into inert biomaterial as well as propagation in defined culture conditions leads to transdifferentiation of ESCs to become sinoatrial node (SAN) pacemaker cells (PCs) [28]. Genomic incorporation TBox3 into ESCs ex vivo leads to generation of PCs-like cells; those express activated leukocyte cells adhesion molecules (ALCAM) and exhibit similarity to PCs for gene expression and immune functions [28]. Transplantation of PCs can restore pacemaker functions of the ailing heart [28]. In summary, ESCs can be transdifferentiated into any kinds of cells representing three germ layers of the body, being most promising source of regenerative medicine for tissue regeneration and disease therapy (). Ethical concerns limit the applications of ESCs, where set guidelines need to be followed; in that case TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs can be explored as alternatives.

TSPSCs maintain tissue homeostasis through continuous cell division, but, unlike ESCs, TSPSCs retain stem cells plasticity and differentiation in tissue specific manner, giving rise to few types of cells (). The number of TSPSCs population to total cells population is too low; in that case their harvesting as well as in vitro manipulation is really a tricky task [29], to explore them for therapeutic scale. Human body has foundation from various types of TSPSCs; discussing the therapeutic application for all types is not feasible. This section of review discusses therapeutic application of pancreatic progenitor cells (PPCs), dental pulp stem cells (DPSCs), inner ear stem cells (IESCs), intestinal progenitor cells (IPCs), limbal progenitor stem cells (LPSCs), epithelial progenitor stem cells (EPSCs), mesoangioblasts (MABs), spermatogonial stem cells (SSCs), the skin derived precursors (SKPs), and adipose derived stem cells (AdSCs) (; ). During embryogenesis PPCs give rise to insulin-producing -cells. The differentiation of PPCs to become -cells is negatively regulated by insulin [30]. PPCs require active FGF and Notch signalling; growing more rapidly in community than in single cell populations advocates the functional importance of niche effect in self-renewal and transdifferentiation processes. In 3D-scaffold culture system, mice embryo derived PPCs grow into hollow organoid spheres; those finally differentiate into insulin-producing -cell clusters [29]. The DSPSCs, responsible for maintenance of teeth health status, can be sourced from apical papilla, deciduous teeth, dental follicle, and periodontal ligaments, have emerged as regenerative medicine candidate, and might be explored for treatment of various kinds of disease including restoration neurogenic functions in teeth [31, 32]. Expansion of DSPSCs in chemically defined neuronal culture medium transforms them into a mixed population of cholinergic, GABAergic, and glutaminergic neurons; those are known to respond towards acetylcholine, GABA, and glutamine stimulations in vivo. These transformed neuronal cells express nestin, glial fibrillary acidic protein (GFAP), III-tubulin, and voltage gated L-type Ca2+ channels [32]. However, absence of Na+ and K+ channels does not support spontaneous action potential generation, necessary for response generation against environmental stimulus. All together, these primordial neuronal stem cells have possible therapeutic potential for treatment of neurodental problems [32]. Sometimes, brain tumor chemotherapy can cause neurodegeneration mediated cognitive impairment, a condition known as chemobrain [33]. The intrahippocampal transplantation of human derived neuronal stem cells to cyclophosphamide behavioural decremented mice restores cognitive functions in a month time. Here the transplanted stem cells differentiate into neuronal and astroglial lineage, reduce neuroinflammation, and restore microglial functions [33]. Furthermore, transplantation of stem cells, followed by chemotherapy, directs pyramidal and granule-cell neurons of the gyrus and CA1 subfields of hippocampus which leads to reduction in spine and dendritic cell density in the brain. These findings suggest that transplantation of stem cells to cranium restores cognitive functions of the chemobrain [33]. The hair cells of the auditory system produced during development are not postmitotic; loss of hair cells cannot be replaced by inner ear stem cells, due to active state of the Notch signalling [34]. Stimulation of inner ear progenitors with -secretase inhibitor ({"type":"entrez-nucleotide","attrs":{"text":"LY411575","term_id":"1257853995","term_text":"LY411575"}}LY411575) abrogates Notch signalling through activation of transcription factor atonal homologue 1 (Atoh1) and directs transdifferentiation of progenitors into cochlear hair cells [34]. Transplantation of in vitro generated hair cells restores acoustic functions in mice, which can be the potential regenerative medicine candidates for the treatment of deafness [34]. Generation of the hair cells also can be achieved through overexpression of -catenin and Atoh1 in Lrg5+ cells in vivo [35]. Similar to ear progenitors, intestine of the digestive tract also has its own tissue specific progenitor stem cells, mediating regeneration of the intestinal tissue [34, 36]. Dysregulation of the common stem cells signalling pathways, Notch/BMP/TGF-/Wnt, in the intestinal tissue leads to disease. Information on these signalling pathways [37] is critically important in designing therapeutics. Coaxing of the intestinal tissue specific progenitors with immune cells (macrophages), connective tissue cells (myofibroblasts), and probiotic bacteria into 3D-scaffolds of inert biomaterial, crafting biological environment, is suitable for differentiation of progenitors to occupy the crypt-villi structures into these scaffolds [36]. Omental implementation of these crypt-villi structures to dogs enhances intestinal mucosa through regeneration of goblet cells containing intestinal tissue [36]. These intestinal scaffolds are close approach for generation of implantable intestinal tissue, divested by infection, trauma, cancer, necrotizing enterocolitis (NEC), and so forth [36]. In vitro culture conditions cause differentiation of intestinal stem cells to become other types of cells, whereas incorporation of valproic acid and CHIR-99021 in culture conditions avoids differentiation of intestinal stem cells, enabling generation of indefinite pool of stem cells to be used for regenerative applications [38]. The limbal stem cells of the basal limbal epithelium, marked with ABCB5, are essential for regeneration and maintenance of corneal tissue [39]. Functional status of ABCB5 is critical for survival and functional integrity of limbal stem cells, protecting them from apoptotic cell death [39]. Limbal stem cells deficiency leads to replacement of corneal epithelium with visually dead conjunctival tissue, which can be contributed by burns, inflammation, and genetic factors [40]. Transplanted human cornea stem cells to mice regrown into fully functional human cornea, possibly supported by blood eye barrier phenomena, can be used for treatment of eye diseases, where regeneration of corneal tissue is critically required for vision restoration [39]. Muscle degenerative disease like duchenne muscular dystrophy (DMD) can cause extensive thrashing of muscle tissue, where tissue engineering technology can be deployed for functional restoration of tissue through regeneration [41]. Encapsulation of mouse or human derived MABs (engineered to express placental derived growth factor (PDGF)) into polyethylene glycol (PEG) fibrinogen hydrogel and their transplantation beneath the skin at ablated tibialis anterior form artificial muscles, which are functionally similar to those of normal tibialis anterior muscles [41]. The PDGF attracts various cell types of vasculogenic and neurogenic potential to the site of transplantation, supporting transdifferentiation of mesoangioblasts to become muscle fibrils [41]. The therapeutic application of MABs in skeletal muscle regeneration and other therapeutic outcomes has been reviewed by others [42]. One of the most important tissue specific stem cells, the male germline stem cells or spermatogonial stem cells (SSCs), produces spermatogenic lineage through mesenchymal and epithets cells [43] which itself creates niche effect on other cells. In vivo transplantation of SSCs with prostate, skin, and uterine mesenchyme leads to differentiation of these cells to become epithelia of the tissue of origin [43]. These newly formed tissues exhibit all physical and physiological characteristics of prostate and skin and the physical characteristics of prostate, skin, and uterus, express tissue specific markers, and suggest that factors secreted from SSCs lead to lineage conservation which defines the importance of niche effect in regenerative medicine [43]. According to an estimate, more than 100 million people are suffering from the condition of diabetic retinopathy, a progressive dropout of vascularisation in retina that leads to loss of vision [44]. The intravitreal injection of adipose derived stem cells (AdSCs) to the eye restores microvascular capillary bed in mice. The AdSCs from healthy donor produce higher amounts of vasoprotective factors compared to glycemic mice, enabling superior vascularisation [44]. However use of AdSCs for disease therapeutics needs further standardization for cell counts in dose of transplant and monitoring of therapeutic outcomes at population scale [44]. Apart from AdSCs, other kinds of stem cells also have therapeutic potential in regenerative medicine for treatment of eye defects, which has been reviewed by others [45]. Fallopian tubes, connecting ovaries to uterus, are the sites where fertilization of the egg takes place. Infection in fallopian tubes can lead to inflammation, tissue scarring, and closure of the fallopian tube which often leads to infertility and ectopic pregnancies. Fallopian is also the site where onset of ovarian cancer takes place. The studies on origin and etiology of ovarian cancer are restricted due to lack of technical advancement for culture of epithelial cells. The in vitro 3D organoid culture of clinically obtained fallopian tube epithelial cells retains their tissue specificity, keeps cells alive, which differentiate into typical ciliated and secretory cells of fallopian tube, and advocates that ectopic examination of fallopian tube in organoid culture settings might be the ideal approach for screening of cancer [46]. The sustained growth and differentiation of fallopian TSPSCs into fallopian tube organoid depend both on the active state of the Wnt and on paracrine Notch signalling [46]. Similar to fallopian tube stem cells, subcutaneous visceral tissue specific cardiac adipose (CA) derived stem cells (AdSCs) have the potential of differentiation into cardiovascular tissue [47]. Systemic infusion of CA-AdSCs into ischemic myocardium of mice regenerates heart tissue and improves cardiac function through differentiation to endothelial cells, vascular smooth cells, and cardiomyocytes and vascular smooth cells. The differentiation and heart regeneration potential of CA-AdSCs are higher than AdSCs [48], representing CA-AdSCs as potent regenerative medicine candidates for myocardial ischemic therapy [47]. The skin derived precursors (SKPs), the progenitors of dermal papilla/hair/hair sheath, give rise to multiple tissues of mesodermal and/or ectodermal origin such as neurons, Schwann cells, adipocytes, chondrocytes, and vascular smooth muscle cells (VSMCs). VSMCs mediate wound healing and angiogenesis process can be derived from human foreskin progenitor SKPs, suggesting that SKPs derived VSMCs are potential regenerative medicine candidates for wound healing and vasculature injuries treatments [49]. In summary, TSPSCs are potentiated with tissue regeneration, where advancement in organoid culture (; ) technologies defines the importance of niche effect in tissue regeneration and therapeutic outcomes of ex vivo expanded stem cells.

MSCs, the multilineage stem cells, differentiate only to tissue of mesodermal origin, which includes tendons, bone, cartilage, ligaments, muscles, and neurons [50]. MSCs are the cells which express combination of markers: CD73+, CD90+, CD105+, CD11b, CD14, CD19, CD34, CD45, CD79a, and HLA-DR, reviewed elsewhere [50]. The application of MSCs in regenerative medicine can be generalized from ongoing clinical trials, phasing through different state of completions, reviewed elsewhere [90]. This section of review outlines the most recent representative applications of MSCs (; ). The anatomical and physiological characteristics of both donor and receiver have equal impact on therapeutic outcomes. The bone marrow derived MSCs (BMDMSCs) from baboon are morphologically and phenotypically similar to those of bladder stem cells and can be used in regeneration of bladder tissue. The BMDMSCs (CD105+, CD73+, CD34, and CD45), expressing GFP reporter, coaxed with small intestinal submucosa (SIS) scaffolds, augment healing of degenerated bladder tissue within 10wks of the transplantation [51]. The combinatorial CD characterized MACs are functionally active at transplantation site, which suggests that CD characterization of donor MSCs yields superior regenerative outcomes [51]. MSCs also have potential to regenerate liver tissue and treat liver cirrhosis, reviewed elsewhere [91]. The regenerative medicinal application of MSCs utilizes cells in two formats as direct transplantation or first transdifferentiation and then transplantation; ex vivo transdifferentiation of MSCs deploys retroviral delivery system that can cause oncogenic effect on cells. Nonviral, NanoScript technology, comprising utility of transcription factors (TFs) functionalized gold nanoparticles, can target specific regulatory site in the genome effectively and direct differentiation of MSCs into another cell fate, depending on regime of TFs. For example, myogenic regulatory factor containing NanoScript-MRF differentiates the adipose tissue derived MSCs into muscle cells [92]. The multipotency characteristics represent MSCs as promising candidate for obtaining stable tissue constructs through coaxed 3D organoid culture; however heterogeneous distribution of MSCs slows down cell proliferation, rendering therapeutic applications of MSCs. Adopting two-step culture system for MSCs can yield homogeneous distribution of MSCs in biomaterial scaffolds. For example, fetal-MSCs coaxed in biomaterial when cultured first in rotating bioreactor followed with static culture lead to homogeneous distribution of MSCs in ECM components [7]. Occurrence of dental carries, periodontal disease, and tooth injury can impact individual's health, where bioengineering of teeth can be the alternative option. Coaxing of epithelial-MSCs with dental stem cells into synthetic polymer gives rise to mature teeth unit, which consisted of mature teeth and oral tissue, offering multiple regenerative therapeutics, reviewed elsewhere [52]. Like the tooth decay, both human and animals are prone to orthopedic injuries, affecting bones, joint, tendon, muscles, cartilage, and so forth. Although natural healing potential of bone is sufficient to heal the common injuries, severe trauma and tumor-recession can abrogate germinal potential of bone-forming stem cells. In vitro chondrogenic, osteogenic, and adipogenic potential of MSCs advocates therapeutic applications of MSCs in orthopedic injuries [53]. Seeding of MSCs, coaxed into biomaterial scaffolds, at defective bone tissue, regenerates defective bone tissues, within fourwks of transplantation; by the end of 32wks newly formed tissues integrate into old bone [54]. Osteoblasts, the bone-forming cells, have lesser actin cytoskeleton compared to adipocytes and MSCs. Treatment of MSCs with cytochalasin-D causes rapid transportation of G-actin, leading to osteogenic transformation of MSCs. Furthermore, injection of cytochalasin-D to mice tibia also promotes bone formation within a wk time frame [55]. The bone formation processes in mice, dog, and human are fundamentally similar, so outcomes of research on mice and dogs can be directional for regenerative application to human. Injection of MSCs to femur head of Legg-Calve-Perthes suffering dog heals the bone very fast and reduces the injury associated pain [55]. Degeneration of skeletal muscle and muscle cramps are very common to sledge dogs, animals, and individuals involved in adventurous athletics activities. Direct injection of adipose tissue derived MSCs to tear-site of semitendinosus muscle in dogs heals injuries much faster than traditional therapies [56]. Damage effect treatment for heart muscle regeneration is much more complex than regeneration of skeletal muscles, which needs high grade fine-tuned coordination of neurons with muscles. Coaxing of MSCs into alginate gel increases cell retention time that leads to releasing of tissue repairing factors in controlled manner. Transplantation of alginate encapsulated cells to mice heart reduces scar size and increases vascularisation, which leads to restoration of heart functions. Furthermore, transplanted MSCs face host inhospitable inflammatory immune responses and other mechanical forces at transplantation site, where encapsulation of cells keeps them away from all sorts of mechanical forces and enables sensing of host tissue microenvironment, and respond accordingly [57]. Ageing, disease, and medicine consumption can cause hair loss, known as alopecia. Although alopecia has no life threatening effects, emotional catchments can lead to psychological disturbance. The available treatments for alopecia include hair transplantation and use of drugs, where drugs are expensive to afford and generation of new hair follicle is challenging. Dermal papillary cells (DPCs), the specialized MSCs localized in hair follicle, are responsible for morphogenesis of hair follicle and hair cycling. The layer-by-layer coating of DPCs, called GAG coating, consists of coating of geletin as outer layer, middle layer of fibroblast growth factor 2 (FGF2) loaded alginate, and innermost layer of geletin. GAG coating creates tissue microenvironment for DPCs that can sustain immunological and mechanical obstacles, supporting generation of hair follicle. Transplantation of GAG-coated DPCs leads to abundant hair growth and maturation of hair follicle, where GAG coating serves as ECM, enhancing intrinsic therapeutic potential of DPCs [58]. During infection, the inflammatory cytokines secreted from host immune cells attract MSCs to the site of inflammation, which modulates inflammatory responses, representing MSCs as key candidate of regenerative medicine for infectious disease therapeutics. Coculture of macrophages (M) and adipose derived MSCs from Leishmania major (LM) susceptible and resistant mice demonstrates that AD-MSCs educate M against LM infection, differentially inducing M1 and M2 phenotype that represents AD-MSC as therapeutic agent for leishmanial therapy [93]. In summary, the multilineage differentiation potential of MSCs, as well as adoption of next-generation organoid culture system, avails MSCs as ideal regenerative medicine candidate.

Umbilical cord, generally thrown at the time of child birth, is the best known source for stem cells, procured in noninvasive manner, having lesser ethical constraints than ESCs. Umbilical cord is rich source of hematopoietic stem cells (HSCs) and MSCs, which possess enormous regeneration potential [94] (; ). The HSCs of cord blood are responsible for constant renewal of all types of blood cells and protective immune cells. The proliferation of HSCs is regulated by Musashi-2 protein mediated attenuation of Aryl hydrocarbon receptor (AHR) signalling in stem cells [95]. UCSCs can be cryopreserved at stem cells banks (; ), in operation by both private and public sector organization. Public stem cells banks operate on donation formats and perform rigorous screening for HLA typing and donated UCSCs remain available to anyone in need, whereas private stem cell banks operation is more personalized, availing cells according to donor consent. Stem cell banking is not so common, even in developed countries. Survey studies find that educated women are more eager to donate UCSCs, but willingness for donation decreases with subsequent deliveries, due to associated cost and safety concerns for preservation [96]. FDA has approved five HSCs for treatment of blood and other immunological complications [97]. The amniotic fluid, drawn during pregnancy for standard diagnostic purposes, is generally discarded without considering its vasculogenic potential. UCSCs are the best alternatives for those patients who lack donors with fully matched HLA typing for peripheral blood and PBMCs and bone marrow [98]. One major issue with UCSCs is number of cells in transplant, fewer cells in transplant require more time for engraftment to mature, and there are also risks of infection and mortality; in that case ex vivo propagation of UCSCs can meet the demand of desired outcomes. There are diverse protocols, available for ex vivo expansion of UCSCs, reviewed elsewhere [99]. Amniotic fluid stem cells (AFSCs), coaxed to fibrin (required for blood clotting, ECM interactions, wound healing, and angiogenesis) hydrogel and PEG supplemented with vascular endothelial growth factor (VEGF), give rise to vascularised tissue, when grafted to mice, suggesting that organoid cultures of UCSCs have promise for generation of biocompatible tissue patches, for treating infants born with congenital heart defects [59]. Retroviral integration of OCT4, KLF4, cMYC, and SOX2 transforms AFSCs into pluripotency stem cells known as AFiPSCs which can be directed to differentiate into extraembryonic trophoblast by BMP2 and BMP4 stimulation, which can be used for regeneration of placental tissues [60]. Wharton's jelly (WJ), the gelatinous substance inside umbilical cord, is rich in mucopolysaccharides, fibroblast, macrophages, and stem cells. The stem cells from UCB and WJ can be transdifferentiated into -cells. Homogeneous nature of WJ-SCs enables better differentiation into -cells; transplantation of these cells to streptozotocin induced diabetic mice efficiently brings glucose level to normal [7]. Easy access and expansion potential and plasticity to differentiate into multiple cell lineages represent WJ as an ideal candidate for regenerative medicine but cells viability changes with passages with maximum viable population at 5th-6th passages. So it is suggested to perform controlled expansion of WJ-MSCS for desired regenerative outcomes [9]. Study suggests that CD34+ expression leads to the best regenerative outcomes, with less chance of host-versus-graft rejection. In vitro expansion of UCSCs, in presence of StemRegenin-1 (SR-1), conditionally expands CD34+ cells [61]. In type I diabetic mellitus (T1DM), T-cell mediated autoimmune destruction of pancreatic -cells occurs, which has been considered as tough to treat. Transplantation of WJ-SCs to recent onset-T1DM patients restores pancreatic function, suggesting that WJ-MSCs are effective in regeneration of pancreatic tissue anomalies [62]. WJ-MSCs also have therapeutic importance for treatment of T2DM. A non-placebo controlled phase I/II clinical trial demonstrates that intravenous and intrapancreatic endovascular injection of WJ-MSCs to T2DM patients controls fasting glucose and glycated haemoglobin through improvement of -cells functions, evidenced by enhanced c-peptides and reduced inflammatory cytokines (IL-1 and IL-6) and T-cells counts [63]. Like diabetes, systematic lupus erythematosus (SLE) also can be treated with WJ-MSCs transplantation. During progression of SLE host immune system targets its own tissue leading to degeneration of renal, cardiovascular, neuronal, and musculoskeletal tissues. A non-placebo controlled follow-up study on 40 SLE patients demonstrates that intravenous infusion of WJ-MSC improves renal functions and decreases systematic lupus erythematosus disease activity index (SLEDAI) and British Isles Lupus Assessment Group (BILAG), and repeated infusion of WJ-MSCs protects the patient from relapse of the disease [64]. Sometimes, host inflammatory immune responses can be detrimental for HSCs transplantation and blood transfusion procedures. Infusion of WJ-MSC to patients, who had allogenic HSCs transplantation, reduces haemorrhage inflammation (HI) of bladder, suggesting that WJ-MSCs are potential stem cells adjuvant in HSCs transplantation and blood transfusion based therapies [100]. Apart from WJ, umbilical cord perivascular space and cord vein are also rich source for obtaining MSCs. The perivascular MSCs of umbilical cord are more primitive than WJ-MSCs and other MSCs from cord suggest that perivascular MSCs might be used as alternatives for WJ-MSCs for regenerative therapeutics outcome [101]. Based on origin, MSCs exhibit differential in vitro and in vivo properties and advocate functional characterization of MSCs, prior to regenerative applications. Emerging evidence suggests that UCSCs can heal brain injuries, caused by neurodegenerative diseases like Alzheimer's, Krabbe's disease, and so forth. Krabbe's disease, the infantile lysosomal storage disease, occurs due to deficiency of myelin synthesizing enzyme (MSE), affecting brain development and cognitive functions. Progression of neurodegeneration finally leads to death of babies aged two. Investigation shows that healing of peripheral nervous system (PNS) and central nervous system (CNS) tissues with Krabbe's disease can be achieved by allogenic UCSCs. UCSCs transplantation to asymptomatic infants with subsequent monitoring for 46 years reveals that UCSCs recover babies from MSE deficiency, improving myelination and cognitive functions, compared to those of symptomatic babies. The survival rate of transplanted UCSCs in asymptomatic and symptomatic infants was 100% and 43%, respectively, suggesting that early diagnosis and timely treatment are critical for UCSCs acceptance for desired therapeutic outcomes. UCSCs are more primitive than BMSCs, so perfect HLA typing is not critically required, representing UCSCs as an excellent source for treatment of all the diseases involving lysosomal defects, like Krabbe's disease, hurler syndrome, adrenoleukodystrophy (ALD), metachromatic leukodystrophy (MLD), Tay-Sachs disease (TSD), and Sandhoff disease [65]. Brain injuries often lead to cavities formation, which can be treated from neuronal parenchyma, generated ex vivo from UCSCs. Coaxing of UCSCs into human originated biodegradable matrix scaffold and in vitro expansion of cells in defined culture conditions lead to formation of neuronal organoids, within threewks' time frame. These organoids structurally resemble brain tissue and consisted of neuroblasts (GFAP+, Nestin+, and Ki67+) and immature stem cells (OCT4+ and SOX2+). The neuroblasts of these organoids further can be differentiated into mature neurons (MAP2+ and TUJ1+) [66]. Administration of high dose of drugs in divesting neuroblastoma therapeutics requires immediate restoration of hematopoiesis. Although BMSCs had been promising in restoration of hematopoiesis UCSCs are sparely used in clinical settings. A case study demonstrates that neuroblastoma patients who received autologous UCSCs survive without any associated side effects [12]. During radiation therapy of neoplasm, spinal cord myelitis can occur, although occurrence of myelitis is a rare event and usually such neurodegenerative complication of spinal cord occurs 624 years after exposure to radiations. Transplantation of allogenic UC-MSCs in laryngeal patients undergoing radiation therapy restores myelination [102]. For treatment of neurodegenerative disease like Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), traumatic brain injuries (TBI), Parkinson's, SCI, stroke, and so forth, distribution of transplanted UCSCs is critical for therapeutic outcomes. In mice and rat, injection of UCSCs and subsequent MRI scanning show that transplanted UCSCs migrate to CNS and multiple peripheral organs [67]. For immunomodulation of tumor cells disease recovery, transplantation of allogenic DCs is required. The CD11c+DCs, derived from UCB, are morphologically and phenotypically similar to those of peripheral blood derived CTLs-DCs, suggesting that UCB-DCs can be used for personalized medicine of cancer patient, in need for DCs transplantation [103]. Coculture of UCSCs with radiation exposed human lung fibroblast stops their transdifferentiation, which suggests that factors secreted from UCSCs may restore niche identity of fibroblast, if they are transplanted to lung after radiation therapy [104]. Tearing of shoulder cuff tendon can cause severe pain and functional disability, whereas ultrasound guided transplantation of UCB-MSCs in rabbit regenerates subscapularis tendon in fourwks' time frame, suggesting that UCB-MSCs are effective enough to treat tendons injuries when injected to focal points of tear-site [68]. Furthermore, transplantation of UCB-MSCs to chondral cartilage injuries site in pig knee along with HA hydrogel composite regenerates hyaline cartilage [69], suggesting that UCB-MSCs are effective regenerative medicine candidate for treating cartilage and ligament injuries. Physiologically circulatory systems of brain, placenta, and lungs are similar. Infusion of UCB-MSCs to preeclampsia (PE) induced hypertension mice reduces the endotoxic effect, suggesting that UC-MSCs are potential source for treatment of endotoxin induced hypertension during pregnancy, drug abuse, and other kinds of inflammatory shocks [105]. Transplantation of UCSCs to severe congenital neutropenia (SCN) patients restores neutrophils count from donor cells without any side effect, representing UCSCs as potential alternative for SCN therapy, when HLA matched bone marrow donors are not accessible [106]. In clinical settings, the success of myocardial infarction (MI) treatment depends on ageing, systemic inflammation in host, and processing of cells for infusion. Infusion of human hyaluronan hydrogel coaxed UCSCs in pigs induces angiogenesis, decreases scar area, improves cardiac function at preclinical level, and suggests that the same strategy might be effective for human [107]. In stem cells therapeutics, UCSCs transplantation can be either autologous or allogenic. Sometimes, the autologous UCSCs transplants cannot combat over tumor relapse, observed in Hodgkin's lymphoma (HL), which might require second dose transplantation of allogenic stem cells, but efficacy and tolerance of stem cells transplant need to be addressed, where tumor replace occurs. A case study demonstrates that second dose allogenic transplants of UCSCs effective for HL patients, who had heavy dose in prior transplant, increase the long term survival chances by 30% [10]. Patients undergoing long term peritoneal renal dialysis are prone to peritoneal fibrosis and can change peritoneal structure and failure of ultrafiltration processes. The intraperitoneal (IP) injection of WJ-MSCs prevents methylglyoxal induced programmed cell death and peritoneal wall thickening and fibrosis, suggesting that WJ-MSCs are effective in therapeutics of encapsulating peritoneal fibrosis [70]. In summary, UCB-HSCs, WJ-MSCs, perivascular MSCs, and UCB-MSCs have tissue regeneration potential.

Bone marrow found in soft spongy bones is responsible for formation of all peripheral blood and comprises hematopoietic stem cells (producing blood cells) and stromal cells (producing fat, cartilage, and bones) [108] (; ). Visually bone marrow has two types, red marrow (myeloid tissue; producing RBC, platelets, and most of WBC) and yellow marrow (producing fat cells and some WBC) [108]. Imbalance in marrow composition can culminate to the diseased condition. Since 1980, bone marrow transplantation is widely accepted for cancer therapeutics [109]. In order to avoid graft rejection, HLA typing of donors is a must, but completely matched donors are limited to family members, which hampers allogenic transplantation applications. Since matching of all HLA antigens is not critically required, in that case defining the critical antigens for haploidentical allogenic donor for patients, who cannot find fully matched donor, might relieve from donor constraints. Two-step administration of lymphoid and myeloid BMSCs from haploidentical donor to the patients of aplastic anaemia and haematological malignancies reconstructs host immune system and the outcomes are almost similar to fully matched transplants, which recommends that profiling of critically important HLA is sufficient for successful outcomes of BMSCs transplantation. Haploidentical HLA matching protocol is the major process for minorities and others who do not have access to matched donor [71]. Furthermore, antigen profiling is not the sole concern for BMSCs based therapeutics. For example, restriction of HIV1 (human immune deficiency virus) infection is not feasible through BMSCs transplantation because HIV1 infection is mediated through CD4+ receptors, chemokine CXC motif receptor 4 (CXCR4), and chemokine receptor 5 (CCR5) for infecting and propagating into T helper (Th), monocytes, macrophages, and dendritic cells (DCs). Genetic variation in CCR2 and CCR5 receptors is also a contributory factor; mediating protection against infection has been reviewed elsewhere [110]. Engineering of hematopoietic stem and progenitor cells (HSPCs) derived CD4+ cells to express HIV1 antagonistic RNA, specifically designed for targeting HIV1 genome, can restrict HIV1 infection, through immune elimination of latently infected CD4+ cells. A single dose infusion of genetically modified (GM), HIV1 resistant HSPCs can be the alternative of HIV1 retroviral therapy. In the present scenario stem cells source, patient selection, transplantation-conditioning regimen, and postinfusion follow-up studies are the major factors, which can limit application of HIV1 resistant GM-HSPCs (CD4+) cells application in AIDS therapy [72, 73]. Platelets, essential for blood clotting, are formed from megakaryocytes inside the bone marrow [74]. Due to infection, trauma, and cancer, there are chances of bone marrow failure. To an extent, spongy bone marrow microenvironment responsible for lineage commitment can be reconstructed ex vivo [75]. The ex vivo constructed 3D-scaffolds consisted of microtubule and silk sponge, flooded with chemically defined organ culture medium, which mimics bone marrow environment. The coculture of megakaryocytes and embryonic stem cells (ESCs) in this microenvironment leads to generation of functional platelets from megakaryocytes [75]. The ex vivo 3D-scaffolds of bone microenvironment can stride the path for generation of platelets in therapeutic quantities for regenerative medication of burns [75] and blood clotting associated defects. Accidents, traumatic injuries, and brain stroke can deplete neuronal stem cells (NSCs), responsible for generation of neurons, astrocytes, and oligodendrocytes. Brain does not repopulate NSCs and heal traumatic injuries itself and transplantation of BMSCs also can heal neurodegeneration alone. Lipoic acid (LA), a known pharmacological antioxidant compound used in treatment of diabetic and multiple sclerosis neuropathy when combined with BMSCs, induces neovascularisation at focal cerebral injuries, within 8wks of transplantation. Vascularisation further attracts microglia and induces their colonization into scaffold, which leads to differentiation of BMSCs to become brain tissue, within 16wks of transplantation. In this approach, healing of tissue directly depends on number of BMSCs in transplantation dose [76]. Dental caries and periodontal disease are common craniofacial disease, often requiring jaw bone reconstruction after removal of the teeth. Traditional therapy focuses on functional and structural restoration of oral tissue, bone, and teeth rather than biological restoration, but BMSCs based therapies promise for regeneration of craniofacial bone defects, enabling replacement of missing teeth in restored bones with dental implants. Bone marrow derived CD14+ and CD90+ stem and progenitor cells, termed as tissue repair cells (TRC), accelerate alveolar bone regeneration and reconstruction of jaw bone when transplanted in damaged craniofacial tissue, earlier to oral implants. Hence, TRC therapy reduces the need of secondary bone grafts, best suited for severe defects in oral bone, skin, and gum, resulting from trauma, disease, or birth defects [77]. Overall, HSCs have great value in regenerative medicine, where stem cells transplantation strategies explore importance of niche in tissue regeneration. Prior to transplantation of BMSCs, clearance of original niche from target tissue is necessary for generation of organoid and organs without host-versus-graft rejection events. Some genetic defects can lead to disorganization of niche, leading to developmental errors. Complementation with human blastocyst derived primary cells can restore niche function of pancreas in pigs and rats, which defines the concept for generation of clinical grade human pancreas in mice and pigs [111]. Similar to other organs, diaphragm also has its own niche. Congenital defects in diaphragm can affect diaphragm functions. In the present scenario functional restoration of congenital diaphragm defects by surgical repair has risk of reoccurrence of defects or incomplete restoration [8]. Decellularization of donor derived diaphragm offers a way for reconstruction of new and functionally compatible diaphragm through niche modulation. Tissue engineering technology based decellularization of diaphragm and simultaneous perfusion of bone marrow mesenchymal stem cells (BM-MSCs) facilitates regeneration of functional scaffolds of diaphragm tissues [8]. In vivo replacement of hemidiaphragm in rats with reseeded scaffolds possesses similar myography and spirometry as it has in vivo in donor rats. These scaffolds retaining natural architecture are devoid of immune cells, retaining intact extracellular matrix that supports adhesion, proliferation, and differentiation of seeded cells [8]. These findings suggest that cadaver obtained diaphragm, seeded with BM-MSCs, can be used for curing patients in need for restoration of diaphragm functions (; ). However, BMSCs are heterogeneous population, which might result in differential outcomes in clinical settings; however clonal expansion of BMSCs yields homogenous cells population for therapeutic application [8]. One study also finds that intracavernous delivery of single clone BMSCs can restore erectile function in diabetic mice [112] and the same strategy might be explored for adult human individuals. The infection of hepatitis C virus (HCV) can cause liver cirrhosis and degeneration of hepatic tissue. The intraparenchymal transplantation of bone marrow mononuclear cells (BMMNCs) into liver tissue decreases aspartate aminotransferase (AST), alanine transaminase (ALT), bilirubin, CD34, and -SMA, suggesting that transplanted BMSCs restore hepatic functions through regeneration of hepatic tissues [113]. In order to meet the growing demand for stem cells transplantation therapy, donor encouragement is always required [8]. The stem cells donation procedure is very simple; with consent donor gets an injection of granulocyte-colony stimulating factor (G-CSF) that increases BMSCs population. Bone marrow collection is done from hip bone using syringe in 4-5hrs, requiring local anaesthesia and within a wk time frame donor gets recovered donation associated weakness.

The field of iPSCs technology and research is new to all other stem cells research, emerging in 2006 when, for the first time, Takahashi and Yamanaka generated ESCs-like cells through genetic incorporation of four factors, Sox2, Oct3/4, Klf4, and c-Myc, into skin fibroblast [3]. Due to extensive nuclear reprogramming, generated iPSCs are indistinguishable from ESCs, for their transcriptome profiling, epigenetic markings, and functional competence [3], but use of retrovirus in transdifferentiation approach has questioned iPSCs technology. Technological advancement has enabled generation of iPSCs from various kinds of adult cells phasing through ESCs or direct transdifferentiation. This section of review outlines most recent advancement in iPSC technology and regenerative applications (; ). Using the new edge of iPSCs technology, terminally differentiated skin cells directly can be transformed into kidney organoids [114], which are functionally and structurally similar to those of kidney tissue in vivo. Up to certain extent kidneys heal themselves; however natural regeneration potential cannot meet healing for severe injuries. During kidneys healing process, a progenitor stem cell needs to become 20 types of cells, required for waste excretion, pH regulation, and restoration of water and electrolytic ions. The procedure for generation of kidney organoids ex vivo, containing functional nephrons, has been identified for human. These ex vivo kidney organoids are similar to fetal first-trimester kidneys for their structure and physiology. Such kidney organoids can serve as model for nephrotoxicity screening of drugs, disease modelling, and organ transplantation. However generation of fully functional kidneys is a far seen event with today's scientific technologies [114]. Loss of neurons in age-related macular degeneration (ARMD) is the common cause of blindness. At preclinical level, transplantation of iPSCs derived neuronal progenitor cells (NPCs) in rat limits progression of disease through generation of 5-6 layers of photoreceptor nuclei, restoring visual acuity [78]. The various approaches of iPSCs mediated retinal regeneration including ARMD have been reviewed elsewhere [79]. Placenta, the cordial connection between mother and developing fetus, gets degenerated in certain pathophysiological conditions. Nuclear programming of OCT4 knock-out (KO) and wild type (WT) mice fibroblast through transient expression of GATA3, EOMES, TFAP2C, and +/ cMYC generates transgene independent trophoblast stem-like cells (iTSCs), which are highly similar to blastocyst derived TSCs for DNA methylation, H3K7ac, nucleosome deposition of H2A.X, and other epigenetic markings. Chimeric differentiation of iTSCs specifically gives rise to haemorrhagic lineages and placental tissue, bypassing pluripotency phase, opening an avenue for generation of fully functional placenta for human [115]. Neurodegenerative disease like Alzheimer's and obstinate epilepsies can degenerate cerebrum, controlling excitatory and inhibitory signals of the brain. The inhibitory tones in cerebral cortex and hippocampus are accounted by -amino butyric acid secreting (GABAergic) interneurons (INs). Loss of these neurons often leads to progressive neurodegeneration. Genomic integration of Ascl1, Dlx5, Foxg1, and Lhx6 to mice and human fibroblast transforms these adult cells into GABAergic-INs (iGABA-INs). These cells have molecular signature of telencephalic INs, release GABA, and show inhibition to host granule neuronal activity [81]. Transplantation of these INs in developing embryo cures from genetic and acquired seizures, where transplanted cells disperse and mature into functional neuronal circuits as local INs [82]. Dorsomorphin and SB-431542 mediated inhibition of TGF- and BMP signalling direct transformation of human iPSCs into cortical spheroids. These cortical spheroids consisted of both peripheral and cortical neurons, surrounded by astrocytes, displaying transcription profiling and electrophysiology similarity with developing fetal brain and mature neurons, respectively [83]. The underlying complex biology and lack of clear etiology and genetic reprogramming and difficulty in recapitulation of brain development have barred understanding of pathophysiology of autism spectrum disorder (ASD) and schizophrenia. 3D organoid cultures of ASD patient derived iPSC generate miniature brain organoid, resembling fetal brain few months after gestation. The idiopathic conditions of these organoids are similar with brain of ASD patients; both possess higher inhibitory GABAergic neurons with imbalanced neuronal connection. Furthermore these organoids express forkhead Box G1 (FOXG1) much higher than normal brain tissue, which explains that FOXG1 might be the leading cause of ASD [84]. Degeneration of other organs and tissues also has been reported, like degeneration of lungs which might occur due to tuberculosis infection, fibrosis, and cancer. The underlying etiology for lung degeneration can be explained through organoid culture. Coaxing of iPSC into inert biomaterial and defined culture leads to formation of lung organoids that consisted of epithelial and mesenchymal cells, which can survive in culture for months. These organoids are miniature lung, resemble tissues of large airways and alveoli, and can be used for lung developmental studies and screening of antituberculosis and anticancer drugs [87]. The conventional multistep reprogramming for iPSCs consumes months of time, while CRISPER-Cas9 system based episomal reprogramming system that combines two steps together enables generation of ESCs-like cells in less than twowks, reducing the chances of culture associated genetic abrasions and unwanted epigenetic [80]. This approach can yield single step ESCs-like cells in more personalized way from adults with retinal degradation and infants with severe immunodeficiency, involving correction for genetic mutation of OCT4 and DNMT3B [80]. The iPSCs expressing anti-CCR5-RNA, which can be differentiated into HIV1 resistant macrophages, have applications in AIDS therapeutics [88]. The diversified immunotherapeutic application of iPSCs has been reviewed elsewhere [89]. The -1 antitrypsin deficiency (A1AD) encoded by serpin peptidase inhibitor clade A member 1 (SERPINA1) protein synthesized in liver protects lungs from neutrophils elastase, the enzyme causing disruption of lungs connective tissue. A1AD deficiency is common cause of both lung and liver disease like chronic obstructive pulmonary disease (COPD) and liver cirrhosis. Patient specific iPSCs from lung and liver cells might explain pathophysiology of A1AD deficiency. COPD patient derived iPSCs show sensitivity to toxic drugs which explains that actual patient might be sensitive in similar fashion. It is known that A1AD deficiency is caused by single base pair mutation and correction of this mutation fixes the A1AD deficiency in hepatic-iPSCs [85]. The high order brain functions, like emotions, anxiety, sleep, depression, appetite, breathing heartbeats, and so forth, are regulated by serotonin neurons. Generation of serotonin neurons occurs prior to birth, which are postmitotic in their nature. Any sort of developmental defect and degeneration of serotonin neurons might lead to neuronal disorders like bipolar disorder, depression, and schizophrenia-like psychiatric conditions. Manipulation of Wnt signalling in human iPSCs in defined culture conditions leads to an in vitro differentiation of iPSCs to serotonin-like neurons. These iPSCs-neurons primarily localize to rhombomere 2-3 segment of rostral raphe nucleus, exhibit electrophysiological properties similar to serotonin neurons, express hydroxylase 2, the developmental marker, and release serotonin in dose and time dependent manner. Transplantation of these neurons might cure from schizophrenia, bipolar disorder, and other neuropathological conditions [116]. The iPSCs technology mediated somatic cell reprogramming of ventricular monocytes results in generation of cells, similar in morphology and functionality with PCs. SA note transplantation of PCs to large animals improves rhythmic heart functions. Pacemaker needs very reliable and robust performance so understanding of transformation process and site of transplantation are the critical aspect for therapeutic validation of iPSCs derived PCs [28]. Diabetes is a major health concern in modern world, and generation of -cells from adult tissue is challenging. Direct reprogramming of skin cells into pancreatic cells, bypassing pluripotency phase, can yield clinical grade -cells. This reprogramming strategy involves transformation of skin cells into definitive endodermal progenitors (cDE) and foregut like progenitor cells (cPF) intermediates and subsequent in vitro expansion of these intermediates to become pancreatic -cells (cPB). The first step is chemically complex and can be understood as nonepisomal reprogramming on day one with pluripotency factors (OCT4, SOX2, KLF4, and hair pin RNA against p53), then supplementation with GFs and chemical supplements on day seven (EGF, bFGF, CHIR, NECA, NaB, Par, and RG), and two weeks later (Activin-A, CHIR, NECA, NaB, and RG) yielding DE and cPF [86]. Transplantation of cPB yields into glucose stimulated secretion of insulin in diabetic mice defines that such cells can be explored for treatment of T1DM and T2DM in more personalized manner [86]. iPSCs represent underrated opportunities for drug industries and clinical research laboratories for development of therapeutics, but safety concerns might limit transplantation applications (; ) [117]. Transplantation of human iPSCs into mice gastrula leads to colonization and differentiation of cells into three germ layers, evidenced with clinical developmental fat measurements. The acceptance of human iPSCs by mice gastrula suggests that correct timing and appropriate reprogramming regime might delimit human mice species barrier. Using this fact of species barrier, generation of human organs in closely associated primates might be possible, which can be used for treatment of genetic factors governed disease at embryo level itself [118]. In summary, iPSCs are safe and effective for treatment of regenerative medicine.

The unstable growth of human population threatens the existence of wildlife, through overexploitation of natural habitats and illegal killing of wild animals, leading many species to face the fate of being endangered and go for extinction. For wildlife conservation, the concept of creation of frozen zoo involves preservation of gene pool and germ plasm from threatened and endangered species (). The frozen zoo tissue samples collection from dead or live animal can be DNA, sperms, eggs, embryos, gonads, skin, or any other tissue of the body [119]. Preserved tissue can be reprogrammed or transdifferentiated to become other types of tissues and cells, which opens an avenue for conservation of endangered species and resurrection of life (). The gonadal tissue from young individuals harbouring immature tissue can be matured in vivo and ex vivo for generation of functional gametes. Transplantation of SSCs to testis of male from the same different species can give rise to spermatozoa of donor cells [120], which might be used for IVF based captive breeding of wild animals. The most dangerous fact in wildlife conservation is low genetic diversity, too few reproductively capable animals which cannot maintain adequate genetic diversity in wild or captivity. Using the edge of iPSC technology, pluripotent stem cells can be generated from skin cells. For endangered drill, Mandrillus leucophaeus, and nearly extinct white rhinoceros, Ceratotherium simum cottoni, iPSC has been generated in 2011 [121]. The endangered animal drill (Mandrillus leucophaeus) is genetically very close to human and often suffers from diabetes, while rhinos are genetically far removed from other primates. The progress in iPSCs, from the human point of view, might be transformed for animal research for recapturing reproductive potential and health in wild animals. However, stem cells based interventions in wild animals are much more complex than classical conservation planning and biomedical research has to face. Conversion of iPSC into egg or sperm can open the door for generation of IVF based embryo; those might be transplanted in womb of live counterparts for propagation of population. Recently, iPSCs have been generated for snow leopard (Panthera uncia), native to mountain ranges of central Asia, which belongs to cat family; this breakthrough has raised the possibilities for cryopreservation of genetic material for future cloning and other assisted reproductive technology (ART) applications, for the conservation of cat species and biodiversity. Generation of leopard iPSCs has been achieved through retroviral-system based genomic integration of OCT4, SOX2, KLF4, cMYC, and NANOG. These iPSCs from snow leopard also open an avenue for further transformation of iPSCs into gametes [122]. The in vivo maturation of grafted tissue depends both on age and on hormonal status of donor tissue. These facts are equally applicable to accepting host. Ectopic xenografts of cryopreserved testis tissue from Indian spotted deer (Moschiola indica) to nude mice yielded generation of spermatocytes [123], suggesting that one-day procurement of functional sperm from premature tissue might become a general technique in wildlife conservation. In summary, tissue biopsies from dead or live animals can be used for generation of iPSCs and functional gametes; those can be used in assisted reproductive technology (ART) for wildlife conservation.

The spectacular progress in the field of stem cells research represents great scope of stem cells regenerative therapeutics. It can be estimated that by 2020 or so we will be able to produce wide array of tissue, organoid, and organs from adult stem cells. Inductions of pluripotency phenotypes in terminally differentiated adult cells have better therapeutic future than ESCs, due to least ethical constraints with adult cells. In the coming future, there might be new pharmaceutical compounds; those can activate tissue specific stem cells, promote stem cells to migrate to the side of tissue injury, and promote their differentiation to tissue specific cells. Except few countries, the ongoing financial and ethical hindrance on ESCs application in regenerative medicine have more chance for funding agencies to distribute funding for the least risky projects on UCSCs, BMSCs, and TSPSCs from biopsies. The existing stem cells therapeutics advancements are more experimental and high in cost; due to that application on broad scale is not feasible in current scenario. In the near future, the advancements of medical science presume using stem cells to treat cancer, muscles damage, autoimmune disease, and spinal cord injuries among a number of impairments and diseases. It is expected that stem cells therapies will bring considerable benefits to the patients suffering from wide range of injuries and disease. There is high optimism for use of BMSCs, TSPSCs, and iPSCs for treatment of various diseases to overcome the contradictions associated with ESCs. For advancement of translational application of stem cells, there is a need of clinical trials, which needs funding rejoinder from both public and private organizations. The critical evaluation of regulatory guidelines at each phase of clinical trial is a must to comprehend the success and efficacy in time frame.

Dr. Anuradha Reddy from Centre for Cellular and Molecular Biology Hyderabad and Mrs. Sarita Kumari from Department of Yoga Science, BU, Bhopal, India, are acknowledged for their critical suggestions and comments on paper.

There are no competing interests associated with this paper.

View post:
Stem Cells Applications in Regenerative Medicine and ...

Cardiac Stem Cells Comments Off on Stem Cells Applications in Regenerative Medicine and … | December 23rd, 2021

DUBLIN, Dec. 20, 2021 /PRNewswire/ -- The "22q11.2 Deletion Syndrome - Global Market Insights, Epidemiology and Forecast to 2030" report has been added to ResearchAndMarkets.com's offering.

This report delivers an in-depth understanding of the 22q11.2 deletion syndrome, historical and forecasted epidemiology as well as the 22q11.2 deletion syndrome market trends in the United States, EU5 (Germany, France, Italy, Spain, and the United Kingdom), and Japan.

Epidemiology

The 22q11.2 deletion syndrome epidemiology division provides the insights about historical and current 22q11.2 deletion syndrome patient pool and forecasted trend for each seven major countries. It helps to recognize the causes of current and forecasted trends by exploring numerous studies and views of key opinion leaders. This part of The report also provides the diagnosed patient pool and their trends along with assumptions undertaken.

Key Findings

The disease epidemiology covered in the report provides historical as well as forecasted 22q11.2 deletion syndrome epidemiology [segmented as Total Prevalent Cases of 22q11.2 deletion syndrome, Total Diagnosed Prevalent Cases of 22q11.2 deletion syndrome, Total diagnosed prevalent cases of 22q11.2 deletion syndrome by age group, Total diagnosed prevalent cases of 22q11.2 deletion syndrome with Behavioral and Psychiatric phenotypes, and Total treated cases of 22q11.2 deletion syndrome with behavioral and psychiatric phenotypes scenario of 22q11.2 deletion syndrome in the 7MM covering United States, EU5 countries (Germany, France, Italy, Spain, and United Kingdom), and Japan from 2018 to 2030.

Country-Wise Epidemiology

In 2020, the total prevalent cases of 22q11.2 deletion syndrome were 196,476 in the 7MM. The United States, in the same year, accounted for 83,326 cases, the highest prevalence of 22q11.2 deletion syndrome cases in the 7MM, accounting for approximately 42% of the total 7MM cases in 2020.

Among the EU-5 countries, the highest number of cases of 22q11.2 deletion syndrome were in Germany and the least in Spain in 2020.

22q11.2 deletion syndrome is often underdiagnosed and misdiagnosed, as the symptoms vary from patient to patient. In the EU-5 countries, the total diagnosed prevalent cases of 22q11.2 deletion syndrome were 35,203 in 2020.

In the year 2020, Japan accounted for 1,409, 1,160, 2,196, 582, and 850 cases for the age groups Infant, 1-5, 6-12, 13-17, and ?18 years, respectively, for 22q11.2 deletion syndrome which are expected to rise during the forecast period.

22q11.2 deletion syndrome is a multisystem disorder characterized by several physical, behavioral and psychiatric disorders. In the 7MM, of the focused age-group 6 to 12 and 13 to 17 years, the diagnosed prevalent cases of 22q11.2 deletion syndrome with Behavioral and Psychiatric Phenotypes were 36,702, in 2020.

Drug Chapters

Drug chapter segment of the 22q11.2 deletion syndrome report encloses the detailed analysis of 22q11.2 deletion syndrome pipeline drugs. It also helps to understand the 22q11.2 deletion syndrome clinical trial details, expressive pharmacological action, agreements and collaborations, approval and patent details, advantages and disadvantages of each included drug and the latest news and press releases.

Emerging Drugs

Zygel (ZYN002; Cannabidiol): Zynerba Pharmaceuticals

Zygel (ZYN002), developed by Zynerba Pharmaceuticals, is the first and only pharmaceutically produced Cannabidiol (CBD). Zygel is formulated as a patent-protected permeation-enhanced gel for transdermal delivery through skin and then into the circulatory system. Zynerba Pharmaceuticals is currently developing the Zygel in Phase II (ACTRN12619000673145; INSPIRE) of the clinical development in Children and Adolescents with 22q11.2 Deletion Syndrome. The trial is currently registered with the Australian New Zealand Clinical Trials Registry (ANZCTR).

RVT-802: Enzyvant/Roivant Sciences/Sumitomo Dainippon Pharma

RVT-802 is a one-time regenerative therapy and is a cultured human thymus tissue engineered to generate a functioning immune response when implanted in pediatric patients with congenital athymia. RVT-802 is a human thymus tissue that has been removed during pediatric cardiac surgery for unrelated conditions. In a healthy, functioning immune system, T cells that start as stem cells in the bone marrow become fully developed in the thymus. Currently, RVT-802 is being developed by Sumitomo Dainippon Pharma (Parent company of Sumitovant Biopharma for Pediatric Congenital Athymia) associated with multiple conditions, including complete DiGeorge Anomaly (cDGA).

Key Findings

The 22q11.2 deletion syndrome market size in the 7MM is expected to change during the forecast period (2021-2030), at a CAGR of 41.9%. According to the estimates, the highest market size of 22q11.2 deletion syndrome is found in the United States.

US: Market Outlook

In United States, the total market size of 22q11.2 deletion syndrome is expected to increase at a CAGR of 43.9% during the study period (2018-2030).

EU-5 Countries: Market Outlook

In the EU-5 countries, the total market size of 22q11.2 deletion syndrome is expected to increase at a CAGR of 37.1% during the study period (2018-2030).

Japan: Market Outlook

In the Japan, the total market size of 22q11.2 deletion syndrome is expected to increase at a CAGR of 41.6% during the study period (2018-2030).

Pipeline Activities

The drugs which are in pipeline include:

Analysts Insight

At present, like many other rare diseases, there is no cure for 22q11.2 deletion syndrome. It is worth mentioning that as a result of the early diagnosis in cases like heart and palate defects, evidence-based protocols can be followed in the early stages of diagnosis to improve the quality of life for children. In such cases, surgery is the major option. The major treatment challenge is seen in patients with psychopathologies (such as Autism, Anxiety disorders, Psychotic disorder [Schizophrenia], Attention deficit hyperactivity disorder [ADHD], and Mood Disorders). In such cases diagnosis is also a major challenge. Antidepressants, antipsychotics, and stimulants are used as off-label therapeutic choices to address all of the aforementioned behavioral and psychiatric traits. Behavioral therapy, on the other hand, is another important part of the treatment process. The pipeline for 22q11.2 deletion syndrome is not competitive, and if Zygel (ZYN002) gets approved by regulatory authorities in the coming years, the overall market size in the seven major markets is likely to grow, as there will be no expected competition.

Access and Reimbursement Scenario

Children are born with this disorder, they require a lifetime of expenditure over diagnosis, treatment, and other supportive care. In a study by Peter et al. (2017), the average pediatric medical care cost associated with the diagnosis of 22q11.2 deletion syndrome in the general population was estimated to be USD 727,178. Costs were highest for patients ascertained prenatally (USD 2,599,955) or in the first year of life (USD 1,043,096), those with cardiac abnormalities or referred for cardiac evaluation (USD 751,535), and patients with low T-cell counts (USD 1,382,222), presumably reflecting the fact that more severely affected cases are more likely to have come to attention early, and that they have a larger number of years of accumulated costs.

KOL Views

To keep up with current market trends, the publisher takes KOLs and SME's opinion working in 22q11.2 deletion syndrome domain through primary research to fill the data gaps and validate our secondary research. Their opinion helps to understand and validate current and emerging therapies treatment patterns o r22q11.2 deletion syndrome market trend. This will support the clients in potential upcoming novel treatment by identifying the overall scenario of the market and the unmet needs.

Competitive Intelligence Analysis

The publisher performs Competitive and Market Intelligence analysis of the 22q11.2 deletion syndrome Market by using various Competitive Intelligence tools that includes - SWOT analysis, PESTLE analysis, Porter's five forces, BCG Matrix, Market entry strategies etc. The inclusion of the analysis entirely depends upon the data availability.

For more information about this report visit https://www.researchandmarkets.com/r/bs6hd4

Media Contact:

Research and Markets Laura Wood, Senior Manager [emailprotected]

For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900

U.S. Fax: 646-607-1907 Fax (outside U.S.): +353-1-481-1716

SOURCE Research and Markets

Original post:
In-depth Analysis of the 22q11.2 Deletion Syndrome Market, 2017-2030 - If Zygel (ZYN002) Gets Approved, the Market Will Grow as There Will Be No...

Cardiac Stem Cells Comments Off on In-depth Analysis of the 22q11.2 Deletion Syndrome Market, 2017-2030 – If Zygel (ZYN002) Gets Approved, the Market Will Grow as There Will Be No… | December 23rd, 2021

Image Credit: Supplied

American Hospital Dubai launches the first and only autologous stem cell transplant department in Dubai. It is the first private hospital in the UAE to offer in-housestem cell transplant of patients stem cells, without the need for a donor. The services include laboratory diagnostics, chemotherapy, stem cell mobilisation, collection, storage and re-infusion with individualised care in specialised rooms.

stem cell transplant of patients stem cells, without the need for a donor. The services include laboratory diagnostics, chemotherapy, stem cell mobilisation, collection, storage and re-infusion with individualised care in specialised rooms.

The DHA-licensed stem cell unit is another step forward for American Hospital Dubais comprehensive cancer care programme, established more than 12 years ago.

The unit has a team of European- and US-qualified medical consultants, subspecialists and allied staff, with an international affiliation for multidisciplinary case review and discussions.

The units nurses are highly skilled in Bone Marrow Transplant (BMT) procedures, with experience in apheresis (separating blood components), cellular therapy, and post-transplant care.

The non-surgical transplant procedure is akin to a blood transfusion. It involves stimulating the stem cells, present mainly in bone marrow, by medication to travel out into the blood. This process, called Peripheral Blood Stem Cell collection, is more common in stem cell transplants for cancer treatment than harvesting stem cells directly from the bone marrow for a BMT.

Welcoming the launch, Dr Tarek Dufan, Chief Medical Officer, American Hospital Dubai, said, The stem cell transplant unit is another milestone in American Hospital Dubais commitment to delivering the most advanced healthcare to UAE and the region. Our cutting-edge Cancer Care Department has been a leader in oncology, and the stem cell unit expands our expertise in offering the latest cancer treatments and management.

Dr Maroun El Khoury, Director of Cancer Centre, said, American Hospital Dubais autologous stem cell transplant unit is the only one of its kind in the UAE. We have highly trained staff specialised in stem cell transplant and care management, excellent in-house laboratory services, radiation facilities, and psychological support systems to deliver a complete and compassionate care experience for patients.

The unit, led by Dr Shabeeha K. Rana, Consultant Haematologist and Director of Stem Cell Transplantation and Cellular Therapy at American Hospital Dubai, includes Dr Maroun El Khoury, Director of Cancer Centre; Dr Faraz Khan, Consultant Haematologist/Oncologist; Dr Julieta Zuluaga, Specialist Haematology and Stem Cell Transplantation; Dr Mona Tareen, Pain Management/Palliative Care Consultant; and Dr Melanie Schlatter, Clinical Psychologist.

The unit will treat haematological cancers such as multiple myeloma, lymphoma, certain types of leukaemia and amyloidosis (build-up of a rare protein called amyloid in the body). In addition, it will treat non-haematological conditions such as germ cell tumours and autoimmune diseases such as multiple sclerosis, Crohns, and ulcerative colitis.

The unit provides patients with support groups who have undergone stem cell transplants as an invaluable psychological tool. Every opportunity is made available to patients to provide feedback, ask questions, and inform and educate themselves with written material resources and emotional support for pre-and post-treatment phases.

American Hospital Dubais stem cell transplant unit follows strict selection criteria before accepting patients to ensure the highest adherence to care quality, safety and efficacy.

This content comes from Reach by Gulf News, which is the branded content team of GN Media.

Originally posted here:
American Hospital Dubai launches first and only autologous stem cell transplant centre in the UAE - Gulf News

Bone Marrow Stem Cells Comments Off on American Hospital Dubai launches first and only autologous stem cell transplant centre in the UAE – Gulf News | December 10th, 2021

JSP191 is well tolerated with no treatment-related adverse events in dose-escalation study

Single-agent conditioning with JSP191 is associated with engraftment, immune reconstitution, and clinical benefit

REDWOOD CITY, Calif., Dec. 08, 2021 (GLOBE NEWSWIRE) -- Jasper Therapeutics, Inc. (NASDAQ: JSPR), a biotechnology company focused on hematopoietic cell transplant therapies, today announced that data on JSP191 showing long-term benefits of hematopoietic stem cells (HSC) engraftment following targeted single-agent JSP191 conditioning in the treatment of severe combined immunodeficiency (SCID) will be presented at the 2021 American Society of Hematology (ASH) Annual Meeting.

The accepted abstract is published and available on the ASH website here.

Title: JSP191 As a Single-Agent Conditioning Regimen Results in Successful Engraftment, Donor Myeloid Chimerism, and Production of Donor Derived Nave Lymphocytes in Patients with Severe Combined Immunodeficiency (SCID)Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Toxicities; Novel Conditioning Approaches. Hematology Disease Topics & Pathways:Abstract: 554Date and Time: Sunday, December 12, 2021, 4.45 p.m. ET

Our ongoing study shows JSP191 to be well tolerated with no treatment-related adverse events across multiple patients ranging from 3 months to 38 years old, said Kevin N. Heller, M.D., Executive Vice President, Research and Development. In this study six of nine non-IL2RG patients with prior hematopoietic cell transplant (HCT), dosed in the initial JSP191 dose escalation (0.1, 0.3, 0.6 and 1.0 mg/kg), achieved HSC engraftment, nave donor T lymphocyte production, and demonstrated clinical improvement. As this trial continues to enroll, the 0.6 mg/kg dose will continue to be evaluated as the potential recommended Phase 2 dose (RP2D) based on HSC engraftment, clinical outcomes and an optimal half-life allowing for integration within existing transplant protocols. We believe that with these initial successful clinical findings, we are one step closer, and uniquely positioned to deliver a targeted non-genotoxic conditioning agent to patients with SCID.

Story continues

About Jasper Therapeutics

Jasper Therapeutics is a biotechnology company focused on the development of novel curative therapies based on the biology of the hematopoietic stem cell. The company is advancing two potentially groundbreaking programs. JSP191, an anti-CD117 monoclonal antibody, is in clinical development as a conditioning agent that clears hematopoietic stem cells from bone marrow in patients undergoing hematopoietic cell transplantation. It is designed to enable safer and more effective curative allogeneic hematopoietic cell transplants and gene therapies. In parallel, Jasper Therapeutics is advancing its preclinical mRNA engineered hematopoietic stem cell (eHSC) platform, which is designed to overcome key limitations of allogeneic and autologous gene-edited stem cell grafts. Both innovative programs have the potential to transform the field and expand hematopoietic stem cell therapy cures to a greater number of patients with life-threatening cancers, genetic diseases and autoimmune diseases than is possible today. For more information, please visit us at jaspertherapeutics.com.

Forward-Looking Statements

Certain statements included in this press release that are not historical facts are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements are sometimes accompanied by words such as believe, may, will, estimate, continue, anticipate, intend, expect, should, would, plan, predict, potential, seem, seek, future, outlook and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, statements the proposed business combination between AMHC and Jasper Therapeutics, the estimated or anticipated future results and benefits of the combined company following the business combination, including Jasper Therapeutics business strategy, expected cash resources of the combined company and the expected uses thereof, current and prospective product candidates, planned clinical trials and preclinical activities and potential product approvals, as well as the potential for market acceptance of any approved products and the related market opportunity. These statements are based on various assumptions, whether or not identified in this press release, and on the current expectations of the respective management teams of Jasper Therapeutics and AMHC and are not predictions of actual performance. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as, and must not be relied on by an investor as, a guarantee, an assurance, a prediction or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and will differ from assumptions. Many actual events and circumstances are beyond the control of Jasper Therapeutics and AMHC. These forward-looking statements are subject to a number of risks and uncertainties, including general economic, political and business conditions the outcome of any legal proceedings that may be instituted against the parties regarding the Business Combination; the risk that the potential product candidates that Jasper Therapeutics develops may not progress through clinical development or receive required regulatory approvals within expected timelines or at all; risks relating to uncertainty regarding the regulatory pathway for Jasper Therapeutics product candidates; the risk that clinical trials may not confirm any safety, potency or other product characteristics described or assumed in this press release; the risk that Jasper Therapeutics will be unable to successfully market or gain market acceptance of its product candidates; the risk that Jasper Therapeutics product candidates may not be beneficial to patients or successfully commercialized; the risk that Jasper Therapeutics has overestimated the size of the target patient population, their willingness to try new therapies and the willingness of physicians to prescribe these therapies; the effects of competition on Jasper Therapeutics business; the risk that third parties on which Jasper Therapeutics depends for laboratory, clinical development, manufacturing and other critical services will fail to perform satisfactorily; the risk that Jasper Therapeutics business, operations, clinical development plans and timelines, and supply chain could be adversely affected by the effects of health epidemics, including the ongoing COVID-19 pandemic; the risk that Jasper Therapeutics will be unable to obtain and maintain sufficient intellectual property protection for its investigational products or will infringe the intellectual property protection of others; the potential inability of the parties to successfully or timely consummate the proposed transaction; the risk of failure to realize the anticipated benefits of the proposed transaction and other risks and uncertainties indicated from time to time in AMHCs public filings, including its most recent Annual Report on Form 10-K for the year ended December 31, 2020 and the proxy statement/prospectus relating to the proposed transaction, including those under Risk Factors therein, and in AMHCs other filings with the SEC. If any of these risks materialize or AMHCs and Jasper Therapeutics assumptions prove incorrect, actual results could differ materially from the results implied by these forward-looking statements. There may be additional risks that neither AMHC nor Jasper Therapeutics presently know, or that AMHC or Jasper Therapeutics currently believe are immaterial, that could also cause actual results to differ from those contained in the forward-looking statements. In addition, forward-looking statements reflect AMHCs and Jasper Therapeutics expectations, plans or forecasts of future events and views as of the date of this press release. AMHC and Jasper Therapeutics anticipate that subsequent events and developments will cause AMHCs and Jasper Therapeutics assessments to change. However, while AMHC and Jasper Therapeutics may elect to update these forward-looking statements at some point in the future, AMHC and Jasper Therapeutics specifically disclaim any obligation to do so. These forward-looking statements should not be relied upon as representing AMHCs and Jasper Therapeutics assessments of any date subsequent to the date of this press release. Accordingly, undue reliance should not be placed upon the forward-looking statements.

Contacts:John Mullaly (investors)LifeSci Advisors617-429-3548jmullaly@lifesciadvisors.com

Lily Eng (media)Real Chemistry206-661-8627leng@realchemistry.com

Jeet Mahal (investors)Jasper Therapeutics650-549-1403jmahal@jaspertherapeutics.com

Read the original post:
Jasper Therapeutics to Present Data on JSP191 Conditioning in SCID patients at the 2021 American Society of Hematology Annual Meeting - Yahoo Finance

Bone Marrow Stem Cells Comments Off on Jasper Therapeutics to Present Data on JSP191 Conditioning in SCID patients at the 2021 American Society of Hematology Annual Meeting – Yahoo Finance | December 10th, 2021

Fifty years ago a boy was born whose brief life would bring hope for thousands of people diagnosed with blood disease.

Anthony Nolans struggle with deadly Wiskott Aldrich Syndrome and his mum Shirleys tireless campaign to save him by finding a suitable bone marrow donor moved the world.

Shirley established the worlds first register of volunteer donors here in the UK.

Tragically, she never did find a suitable match for Anthony and he died when he was seven years old.

But the register became his legacy, recruiting donors around the world. Their bone marrow and stem cells have saved more than 20,000 patients with leukaemia and other blood disorders.

Alan Corby spent six months in the next isolation room to Anthony at Westminster Childrens Hospital. Neither were expected to survive.

Alan said: Much of the time he was the only person I could see. We would talk and play card games like Twist through the glass.

When I was well enough I moved to my local hospital. I went back to see Anthony a few months later, but he had passed away.

Image:

His life may have been short, but it had an incredible impact. Thousands have been given a second chance of life thanks to him and his mum.

On what would have been Anthonys 50th birthday, the Mirror meets three boys given hope of beating deadly blood diseases by his legacy.

Visit anthonynolan.org for more information or to join the donor register.

Georgie McAvoy knows the heartache Shirley Nolan endured searching for a donor to save her son.

Because her little boy Daniel was born with the same rare disease that killed Anthony.

Daniel, two, has Wiskott Aldrich Syndrome which prevents his blood cells from fighting infection and clotting properly. His only hope is a bone marrow transplant to reset his immune system.

A first transplant in June last year failed as Daniel body rejected his donor cells and relapsed.

Image:

He is now preparing to undergo another gruelling course of chemotherapy, followed by a second transplant and will spend Christmas recovering in hospital.

Georgie, 31, said: We have been through so much, but Daniel is still fighting. He has coped with everything that has been thrown at him and he keeps smiling.

We are so grateful for the donor register and everything that Shirley Nolan did it is the reason that Daniel is still alive.

Daniels parents realised something was wrong when he began suffering nosebleeds and they found blood in his nappy when he was three weeks old.

He then developed sepsis and spent 11 days fighting for his life in intensive care.

Georgie and dad Andrew, 38, even asked the hospital chaplain to christen Daniel is his cot as they feared he might not survive.

Image:

Georgie, from Huntingdon in Cambridge, said: The doctors told us he needed a bone marrow transplant to save his life, but that some children didnt make it to transplant.

It was devastating. We didnt know if he would start to walk or go to school. I remember thinking, I need him to be christened in case something happens.

It was emotional. Daniels big sister Holly wore a christening gown made from my wedding dress and Id planned for Daniel to wear it too, but that obviously wasnt possible.

Daniel was eventually diagnosed with Wiskott-Aldrich syndrome, a rare genetic disorder that affects one in every one million boys, in May last year after an unrelated hernia operation.

Neither his parents nor Holly, four, were a suitable match, so their only hope was to find a donor through the stem cell register, which the charity Anthony Nolan managed within two months.

Image:

Daniel was due to undergo the transplant in March last year, but his procedure was postponed after the Covid pandemic began for fear there would be a shortage of doctors, nurses, or beds.

Georgie said: That was really scary. Daniel had been through all his preparation and we were ready to go, then everything blew up before our eyes. We didnt know what would happen.

Daniel continued to deteriorate, picking up more infections until his transplant finally went ahead at Great Ormond Street Hospital at the end of June as doctors could not risk waiting any longer.

He was only allowed one parent with him as he underwent chemotherapy to remove his immune system ahead of the transplant.

Image:

Daniel returned home in August but suffered a drug relating seizure, then graft versus host disease as his body tried to reject the donor cells and spent last Christmas in hospital.

Georgie said: The last two relapses have been particularly difficult. During the last one he began vomiting digested blood. His stomach had to be drained constantly.

At that point they said there were no more options, we had to do another transplant and we needed a different donor as his body had rejected the first.

It will be hard spending another Christmas in hospital, but we feel so lucky to have found another donor to give Daniel a second chance. That wouldnt have happened without Anthony Nolan.

Time is running out for Alife Pinckney to find a lifesaving stem cell donor.

The eight year-old from Exeter relies on weekly blood transfusions to top up his critically low levels of platelets. That has bought Alfie more time, but his condition is getting worse.

His desperate family know his only hope is a transplant, but his mixed British and Chinese heritage makes it harder to find a matching tissue type to prevent his body rejecting the donor cells.

Image:

Alfies mum Lily, said: Its so hard to watch your child in pain and be incapable of helping. Its tearing me apart. Our only hope is to encourage as many people as possible to join the register.

Alfie developed Aplastic Anaemia when he was five years-old. It means his body cannot produce the platelets he needs for his blood to clot properly and he cannot fight infection.

At the time his British-born parents Lily and Charles were living and working in Hong Kong. They returned to the UK just before lockdown last year to be near family and step up Alfies treatment just like Shirley Nolan moved home from Australia to search for a donor for Anthony.

They hoped they had found a donor earlier this year when a woman in Brazil was confirmed as a matching tissue type, but that fell through.

Image:

Since then, Alfie has continued to deteriorate as his body burns through the weekly platelet transfusions and he suffered a terrifying haemorrhage.

Dad Charles said: He had a huge, uncontrollable nosebleed and bleeding from the gums. He was clutching the kitchen bin, vomiting blood, screaming Daddy, help me.

We rushed him into the high dependency unit and I was mopping blood of his arms, face, and torso as several doctors and nurses tried to keep him alive. It was harrowing.

Its so easy to join the register. It only takes three minutes to swab your checks, then you can get on with your life. But that could help to save Mason or another childs life.

Katie Jordan got the devastating news that little Mason had blood cancer on Christmas Eve last year.

Image:

Image:

The only cure for his Juvenile Myelomonocytic Leukaemia was a bone marrow transplant but mum Katie was not a good match, nor was anyone on the donor register.

Most children with the disease only survive for 12 months after diagnosis. So Katie, a single mum like Shirley, launched her own campaign to save her son.

Masons Mission raised nearly 54,000 for Anthony Nolan, helping the charity to test the backlog of 25,000 swab samples that built up during the pandemic and add them to the donor register.

Katie, from Stockton-on-Tees said: I was living my worst nightmare. It was heartbreaking to think that Christmas could have been our last together.

I would give my life for Mason, but I wasnt a match. So I did everything I could to find a donor.

Image:

Thankfully Anthony Nolan did find a suitable donor two months later and Mason had a successful stem cell transplant in March this year.

He was rushed back to hospital over the summer after developing blisters all over his body and spent a week fighting for his life in intensive care before they subsided.

But the two year-old made a full recovery and is now looking forward to a happy, healthy Christmas.

Katie said: We were lucky that we found a donor so quickly. When they told us, I couldnt stop crying. I would love to meet his donor one day and thank them."

Read More

Read More

View original post here:
The Anthony Nolan legacy: Three boys given hope of beating deadly blood diseases - The Mirror

Bone Marrow Stem Cells Comments Off on The Anthony Nolan legacy: Three boys given hope of beating deadly blood diseases – The Mirror | December 10th, 2021

Report Ocean presents a new report on Mesenchymal Stem Cells Market size, share, growth, industry trends, and forecast 2026, covering various industry elements and growth trends helpful for predicting the markets future. The global mesenchymal stem cells market size to reach USD 2,518.5 Million by 2026, growing at a CAGR of 7.0% during forecast period, according to a new research report published . The report Mesenchymal Stem Cells Market, [By Source (Bone Marrow, Umbilical Cord Blood, Peripheral Blood, Lung Tissue, Synovial Tissues, Amniotic Fluids, Adipose Tissues); By Application (Injuries, Drug Discovery, Cardiovascular Infraction, Others); By Region]: Market Size & Forecast, 2018 2026 provides an extensive analysis of present market dynamics and predicted future trends. The market was valued at USD 1,335.1 million in 2017. In 2017, the drug discovery application dominated the market, in terms of revenue. North America region is observed to be the leading contributor in the global market revenue in 2017.

Request To Download Sample of This Strategic Report@

https://reportocean.com/industry-verticals/sample-request?report_id=31977

In order to produce a holistic assessment of the market, a variety of factors is considered, including demographics, business cycles, and microeconomic factors specific to the market under study. Mesenchymal Stem Cells Market report 2021 also contains a comprehensive business analysis of the state of the business, which analyzes innovative ways for business growth and describes critical factors such as prime manufacturers, production value, key regions, and growth rate.

The Centers for Medicare and Medicaid Services report that US healthcare expenditures grew by 4.6% to US$ 3.8 trillion in 2019, or US$ 11,582 per person, and accounted for 17.7% of GDP. Also, the federal government accounted for 29.0% of the total health expenditures, followed by households (28.4%). State and local governments accounted for 16.1% of total health care expenditures, while other private revenues accounted for 7.5%.

This study aims to define market sizes and forecast the values for different segments and countries in the coming eight years. The study aims to include qualitative and quantitative perspectives about the industry within the regions and countries covered in the report. The report also outlines the significant factors, such as driving factors and challenges, that will determine the markets future growth.

Request To Download Sample of This Strategic Report@

https://reportocean.com/industry-verticals/sample-request?report_id=31977

These stem cells mainly function for the replacement of damaged cell and tissues. The potential of these cell is to heal the damaged tissue with no pain to the individual. Scientists are majorly focusing on developing new and innovative treatment options for the various chronic diseases like cancer. Additionally, the local governments have also taken various steps for promoting the use of these stem cells.

The significant aspects that are increasing the development in market for mesenchymal stem cells consist of enhancing need for these stem cells as an efficient therapy option for knee replacement. Raising senior populace throughout the world, as well as increasing frequency of numerous persistent conditions consisting of cancer cells, autoimmune illness, bone and cartilage diseases are elements anticipated to enhance the market development throughout the forecast period. The mesenchymal stem cells market is obtaining favorable assistance by the reliable federal government policies, as well as funding for R&D activities which is anticipated to influence the market growth over coming years. According to the reports released by world health organization (WHO), by 2050 individuals aged over 60 will certainly make up greater than 20% of the globes population. Of that 20%, a traditional quote of 15% is estimated to have symptomatic OA, as well as one-third of these individuals are expected to be influenced by extreme specials needs. Taking into consideration all these aspects, the market for mesenchymal stem cells will certainly witness a substantial development in the future.

Increasing demand for better healthcare facilities, rising geriatric population across the globe, and continuous research and development activities in this area by the key players is expected to have a positive impact on the growth of Mesenchymal Stem Cells market. North America generated the highest revenue in 2017, and is expected to be the leading region globally during the forecast period. The Asia Pacific market is also expected to witness significant market growth in coming years. Developing healthcare infrastructure among countries such as China, India in this region is observed to be the major factor promoting the growth of this market during the forecast period.

The major key players operating in the industry are Cell Applications, Inc., Cyagen Biosciences Inc. Axol Bioscience Ltd., Cytori Therapeutics Inc., Stem cell technologies Inc., Celprogen, Inc. BrainStorm Cell Therapeutics, Stemedica Cell Technologies, Inc. These companies launch new products and undertake strategic collaboration and partnerships with other companies in this market to expand presence and to meet the increasing needs and requirements of consumers.

Get a Sample PDF copy of the report@

https://reportocean.com/industry-verticals/sample-request?report_id=31977

Polaris Market Research has segmented the global mesenchymal stem cells market on the basis of source type, application and region:

Mesenchymal Stem Cells Source Type Outlook (Revenue, USD Million, 2015 2026)

Bone Marrow

Umbilical Cord Blood

Peripheral Blood

Lung Tissue

Synovial Tissues

Amniotic Fluids

Adipose Tissues

Mesenchymal Stem Cells Application Outlook (Revenue, USD Million, 2015 2026)

Injuries

Drug Discovery

Cardiovascular Infraction

Others

Get a Sample PDF copy of the report@

https://reportocean.com/industry-verticals/sample-request?report_id=31977

Mesenchymal Stem Cells Regional Outlook (Revenue, USD Million, 2015 2026)

North America

U.S.

Canada

Europe

Germany

UK

France

Italy

Spain

Russia

Rest of Europe

Asia-Pacific

China

India

Japan

Singapore

Malaysia

Australia

Rest of Asia-Pacific

Latin America

Mexico

Brazil

Argentina

Rest of LATAM

Middle East & Africa

What are the aspects of this report that relate to regional analysis?

The reports geographical regions include North America, Europe, Asia Pacific, Latin America, the Middle East, and Africa.

The report provides a comprehensive analysis of market trends, including information on usage and consumption at the regional level.

Reports on the market include the growth rates of each region, which includes their countries, over the coming years.

How are the key players in the market assessed?

This report provides a comprehensive analysis of leading competitors in the market.

The report includes information about the key vendors in the market.

The report provides a complete overview of each company, including its profile, revenue generation, cost of goods, and products manufactured.

The report presents the facts and figures about market competitors, alongside the viewpoints of leading market players.

A market report includes details on recent market developments, mergers, and acquisitions involving the key players mentioned.

What is the key information extracted from the report?

Extensive information on factors estimated to affect the Market growth and market share during the forecast period is presented in the report.The report offers the present scenario and future growth prospects Market in various geographical regions.The competitive landscape analysis on the market as well as the qualitative and quantitative information is delivered.The SWOT analysis is conducted along with Porters Five Force analysis.The in-depth analysis provides an insight into the Market, underlining the growth rate and opportunities offered in the business.

Access full Report Description, TOC, Table of Figure, Chart, etc:

https://reportocean.com/industry-verticals/sample-request?report_id=31977

About Report Ocean:

We are the best market research reports provider in the industry. Report Ocean believes in providing quality reports to clients to meet the top line and bottom line goals which will boost your market share in todays competitive environment. Report Ocean is a one-stop solution for individuals, organizations, and industries that are looking for innovative market research reports.

Get in Touch with Us:

Report Ocean:

Email: sales@reportocean.com

Address: 500 N Michigan Ave, Suite 600, Chicago, Illinois 60611 UNITED STATES

Tel: +1 888 212 3539 (US TOLL FREE)

Website: https://www.reportocean.com

Read more:
Mesenchymal Stem Cells Market Growth Drivers 2021, Industry Share-Size, Global Demand, Emerging Trends, Opportunities in Grooming Regions, Key Players...

Bone Marrow Stem Cells Comments Off on Mesenchymal Stem Cells Market Growth Drivers 2021, Industry Share-Size, Global Demand, Emerging Trends, Opportunities in Grooming Regions, Key Players… | December 10th, 2021

What happened

Shares of Longeveron (NASDAQ:LGVN), a clinical-stage biotechnology company headquartered in Miami, are soaring in response to good news from the U.S. Food and Drug Administration (FDA). Investors excited about an orphan drug designation for the company's stem cell treatment pushed the stock 36.7% higher as of 10:37 a.m. ET on Friday.

Longeveron is developing bone marrow-derived mesenchymal stromal cells for the treatment of a variety of age-related disorders including Alzheimer's disease. Today, the FDA granted the company's lead candidate, Lomecel-B, an orphan designation for the treatment of a rare condition called hypoplastic left heart syndrome.

Image source: Getty Images.

Generally, orphan drug designations aren't something to get excited about. The FDA hands them out like candy to just about anyone that intends to develop a drug for underserved patients with a rare condition.

If approved to treat hypoplastic left heart syndrome, this orphan drug designation can begin assisting Longeveron with a handful of useful benefits. The most important one is seven years of market exclusivity.

There isn't much of a difference between the bone marrow-derived stem cells in Lomecel-B and the stem cells biomedical scientists have been researching for decades. They've been renamed medical signaling cells in recent years, but evidence of a significant benefit for specific indications remains elusive.

Longeveron is now a good stock to buy, and betting against it could prove disastrous, too. In the first quarter of 2022, Longeveron intends to begin clinical trials with Lomecel-B as a treatment for Alzheimer's disease.

This article represents the opinion of the writer, who may disagree with the official recommendation position of a Motley Fool premium advisory service. Were motley! Questioning an investing thesis -- even one of our own -- helps us all think critically about investing and make decisions that help us become smarter, happier, and richer.

The rest is here:
Here's Why Longeveron Is Surging Today - Motley Fool

Bone Marrow Stem Cells Comments Off on Here’s Why Longeveron Is Surging Today – Motley Fool | December 10th, 2021

Sanford Health is continuing to explore the potential of orthobiologics and regenerative medicine with a study that may advance treatment for those living with osteoarthritis.

This trial known as ENDURE, which is run in full compliance with the FDA, will examine the safety and effectiveness of adult, adipose (fat)-derived stem cells.

Im really excited to get the trial started, said Donella Herman, M.D., a specialist in sports medicine at Sanford Health. Im even more excited about a year from now because I feel like were just going to learn so much about how effective this treatment is and what it is effective for.

Learn more: Orthopedics regenerative medicine at Sanford Health

Essentially, orthobiologics and regenerative medicine tap into the bodys natural healing ability.

Orthobiologics, a part of regenerative medicine, refers to the use of biological substances found in the body to help treat muscle and bone issues.

This may include injuries to muscles, tendons, and ligaments and as the focus of this trial more chronic conditions such as osteoarthritis.

When used properly by qualified providers, cell therapies are proving to be effective treatment options.

Our goals are to collect data for the different branches of orthobiologics, Dr. Herman said. Do people with knee osteoarthritis respond better with PRP (platelet rich plasma) or bone-marrow derived cells or fat-derived stem cells? Which works best? Which works for the longest time? Thats the kind of information were looking for. Its that kind of ratio that we just dont have right now.

One of the obstacles in regenerative medicine at this point, Dr. Herman said, is that its often being marketed by people with dubious clinical qualifications. They use underdeveloped research and make unfounded claims.

Its become a little bit of a wild, wild west with stem cells and PRP, Dr. Herman said. There are pop-up shops all over the place. Its one thing to have access to these things and allow access to people, but if youre not doing that in a responsible way and using that opportunity to build on a knowledge base, its kind of smoke and mirrors.

In sharp contrast to that scenario, this trial aims to add to the bank of knowledge in regenerative medicine.

We know we can tell people what were putting in their knee or their hip or their shoulder because were testing, Dr. Herman said. A lot of other places theyre just injecting it. They dont know if the stem cells are viable or not.

A typical candidate for the study, as described by Dr. Herman, might have osteoarthritis in their wrist and would not want to sacrifice a loss of motion that could come with surgery. They also would likely have exhausted the steroid injections treatment options that offer temporary relief.

We think of regenerative medicine as a possible alternative therapy that may help people put off surgery, Dr. Herman said. I dont ever tell people it means you will never need surgery but what it does is hopefully buy a little time until youre ready for that. There are lots of times where well do steroid injections until those fail and then they have to get a new joint. Were hoping for this to give us a bridge.

Once a patient is approved to be part of the ENDURE study, the procedure includes:

Follow-ups are then completed in person and over the phone.

Qualified candidates must be 18 or older and:

The cost associated with the study is not currently covered by insurance. By enrolling in the ENDURE study, however, participants may be playing a role in advancing regenerative cell research that could have the potential to improve care for future generations.

Those interested in hearing more about possible eligibility in the study can call (605) 328-3700.

Posted In Innovations, Orthopedics, Research, Specialty Care, Sports Medicine

Originally posted here:
Sanford Health opens study of cell injections for arthritis - Sanford Health News

Bone Marrow Stem Cells Comments Off on Sanford Health opens study of cell injections for arthritis – Sanford Health News | December 10th, 2021

Significance

The recently introduced RNA velocity methods, by leveraging the intrinsic RNA splicing process, have shown their unique capability of identifying the directionality of the cell differentiation trajectory. However, due to the minimal amount of unspliced RNA contents, the estimation of RNA velocity suffers from high noise and may result in less reliable trajectories. Here, we present Velocity Autoencoder (VeloAE), a tailored autoencoder to denoise RNA velocity for more accurate quantification of cell transitions. Through various biological systems, we demonstrate its effectiveness for correcting the inferred trajectory and its interpretability for linking the learned dimensions to underlying biological processes.

RNA velocity is a promising technique for quantifying cellular transitions from single-cell transcriptome experiments and revealing transient cellular dynamics among a heterogeneous cell population. However, the cell transitions estimated from high-dimensional RNA velocity are often unstable or inaccurate, partly due to the high technical noise and less informative projection. Here, we present Velocity Autoencoder (VeloAE), a tailored representation learning method, to learn a low-dimensional representation of RNA velocity on which cellular transitions can be robustly estimated. On various experimental datasets, we show that VeloAE can both accurately identify stimulation dynamics in time-series designs and effectively capture expected cellular differentiation in different biological systems. VeloAE, therefore, enhances the usefulness of RNA velocity for studying a wide range of biological processes.

Author contributions: C.Q. and Y.H. designed research; C.Q. performed research; C.Q. contributed new reagents/analytic tools; C.Q. analyzed data; and C.Q. and Y.H. wrote the paper.

The authors declare no competing interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2105859118/-/DCSupplemental.

VeloAE is an open-source Python package available at GitHub, https://github.com/qiaochen/VeloAE. All the analysis notebooks for reproducing the results are also available in this repository. Previously published data were used for this work (8, 10, 1925).

View post:
Representation learning of RNA velocity reveals robust cell transitions - pnas.org

Bone Marrow Stem Cells Comments Off on Representation learning of RNA velocity reveals robust cell transitions – pnas.org | December 10th, 2021

In the summer of 2015, a 7-year-old named Hassan was admitted to the burn unit of the Ruhr University Childrens Hospital in Bochum, Germany, with red, oozing wounds from head to toe.

It wasnt a fire that took his skin. It was a bacterial infection, resulting from an incurable genetic disorder. Called junctional epidermolysis bullosa, the condition deprives the skin of a protein needed to hold its layers together and leads to large, painful lesions. For kids, its often fatal. And indeed, Hassans doctors told his parents, Syrian refugees who had fled to Germany, the young boy was dying.

The doctors tried one last thing to save him. They cut out a tiny, unblistered patch of skin from the childs groin and sent it to the laboratory of Michele de Luca, an Italian stem cell expert who heads the Center for Regenerative Medicine at the University of Modena and Reggio Emilia. De Lucas team used a viral vector to ferry into Hassans skin cells a functional version of the gene LAMB3, which codes for laminin, the protein that anchors the surface of the skin to the layers below.

advertisement

Then the scientists grew the modified cells into sheets big enough for Ruhr University plastic surgeons Tobias Hirsch and Maximilian Kueckelhaus to graft onto Hassans raw, bedridden body, which they did over the course of that October, November, and the following January.

It worked better than the boys doctors could have imagined. In 2017, de Luca, Hirsch, Kueckelhaus, and their colleagues reported that Hassan was doing well, living like a normal boy in his lab-grown skin. At the time though, there was still a big question on all their minds: How long would it last? Would the transgenic stem cells keep replenishing the skin or would they sputter out? Or worse could they trigger a cascade of cancer-causing reactions?

advertisement

Today, the same team is out with an update. Five years and five months after the initial intervention, Hassan is still, for the most part, thriving in fully functional skin that has grown with the now-teenager. He is attending school, and playing sports with his friends and siblings, though he avoids swimming due to blistering in the areas that werent replaced by the lab-grown skin. One of his favorite activities is a pedal-powered go kart. There are no signs his modified stem cells have lost their steam, and no traces of tumors to be found.

The encouraging follow-up data has been instrumental in moving forward a larger clinical trial of the approach, offering hope to the 500,000 epidermolysis bullosa patients worldwide currently living without treatment options.

We were astonished by the speedy recovery, Kueckelhaus, now at University Hospital Muenster, told STAT via email. But experience from skin transplantation in other settings made him and his colleagues wary of the grafts failing as the months and years wore on. Thankfully, wrote Kueckelhaus, those fears never materialized. We are very happy to be able to prove that none of these complications appeared and the genetically modified skin remains 100% stable. The chances are good that he will be able to live a relatively normal life.

Over the last five years, Hassans team of doctors and researchers has put his new skin through a battery of tests checking it for sensitivity to hot and cold, water retention, pigmentation and hemoglobin levels, and if it had developed all the structures youd expect healthy skin to have, including sweat glands and hair follicles. Across the board, the engineered skin appeared normal, without the need for moisturizers or medical ointments. The only flaw they found was that Hassans skin wasnt as sensitive to fine touch, especially in his lower right leg. This mild neuropathy they attributed not to the graft itself, but to how that limb was prepared doctors used a more aggressive technique that might have damaged the nerves there.

The team also used molecular techniques to trace the cells theyd grown in the lab as they divided and expanded over Hassans body. They found that all the different kinds of cells composing the boys new skin were being generated by a small pool of self-renewing stem cells called holoclone-forming cells, carrying the Italian teams genetic correction.

This was quite an insight into the biology of the epidermis, said de Luca. Its an insight he expects will have huge consequences for any efforts to advance similar gene therapies for treating other diseases affecting the skin. You have to have the holoclone-forming cells in your culture if you want to have long-lasting epidermis, he said.

The approach pioneered by de Lucas team will soon be headed for its biggest clinical test yet, after nearly a decade of fits and starts. They expect to begin recruiting for a multi-center Phase 2/3 trial sometime next year.

De Luca first successfully treated a junctional EB patient in 2005. But then a change to European Union laws governing cell and gene therapies forced his team to stop work while they found ways to comply with the new rules. It took years of paperwork, building a manufacturing facility, and spinning out a small biotech company called Holostem to be ready to begin clinical research again. Hassan came along right as they were gearing up for a Phase 1 trial, but data from the boys case, which was granted approval under a compassionate use provision, convinced regulators that the cell grafts could move to larger, more pivotal trials, according to de Luca.

We didnt cure the disease, he told STAT. But the skin has been restored, basically permanently. We did not observe a single blister in five years. The wound healing is normal, the skin is robust. From this point of view, the quality of life is not even comparable to what it was before.

Original post:
Syrian refugee is thriving five years after last-gasp gene therapy - STAT - STAT

Skin Stem Cells Comments Off on Syrian refugee is thriving five years after last-gasp gene therapy – STAT – STAT | December 10th, 2021

Stem cell therapy, sometimes called regenerative medicine, is one of the most exciting areas of the life sciences sector right now.

Since the pandemic, the sector has emerged into the publics spotlight with new developments in mRNA-based vaccines and therapies.

Nasdaq is the obvious breeding ground for world-class stem cell companies with the likes of Moderna and BioNTech, and lesser known names like Anavex and Enochian.

In Australia, Mesoblast (ASX:MSB) has long been the local poster child for the regenerative medicine industry.

Mesoblast has developed a platform of innovative cellular medicines, but the company has struggled since the FDA rejected its drug in October last year.

Now, other ASX companies like Cynata Therapeutics (ASX:CYP)are making rapid progress to take over the mantle from MSB in this hot field.

Cynata is developing a mesenchymal stem cells (or MSC) technology, which it says has huge therapeutic potential for numerous unmet medical needs.

This includes asthma, heart attack, sepsis, and acute respiratory distress syndrome (ARDS), which all add up to a market opportunity worth $46bn, says the company.

According to CEO Dr Ross Macdonald, who spoke to Stockhead today, MSC is the hottest segment of stem cell therapy at the moment, and has gained a lot of attention recently.

There is a huge interest, and theres been more than 1000 clinical trials conducted around the world using MSC, Dr Macdonald told Stockhead.

He explains that the humans immune system controls many of the bodys functions responsible for repairing tissue after injury or disease, and defending against invading germs like viruses or bacteria.

And just like an orchestral conductor, MSC seems to be playing a central role in that coordination within our immune system.

We now have a firm understanding of how those cells coordinate the bodys responses, and can use that knowledge to enhance those processes that they control, Dr Macdonald explained.

In short, MSC therapies work by expressing a variety of chemokines and cytokines that aid in repair of degraded tissue, restoration of normal tissue metabolism and, most importantly, counteracting inflammation.

And because MSCs play that co-ordination role within the immune system, they can be used to treat different diseases.

However theres one big problem with cell-based therapies, and its not to do with the safety and efficacy.

Its how to manufacture these products on a mass scale, that is the greatest challenge right now, says Dr Macdonald.

Unlike aspirin where it can be synthesised in a chemical lab and produced in bulk, manufacturing a living drug like a cell is a whole lot more complicated.

But that big challenge is the exact area of strength and competitive advantage that Cynata has, Dr Macdonald told Stockhead.

He says Cynata has a technology platform which allows it to manufacture essentially limitless quantities of MSCs, consistently and economically.

Dr Macdonald explains there are two approaches to using cell therapy, the autologous and the allogeneic approach.

The autologous approach is where the patient themselves serves as their own donor.

This is obviously bespoke and inefficient, because the drug can only be manufactured for that one patient, and is obviously not an industrialised process, he said.

But by taking an allogeneic approach, Cynata has the ability to start with a one time donation of cells from one single donor.

Well never have to go back to that human donor ever again, so our process of producing cells has become a very much more typical industrialised process.

The company has a patent for this, with two clinical trials underway and two more under preparation.

A Phase 3 clinical trial for osteoarthritis which is funded by a NHMRC grant has progressed the furthest, while a Phase 2 trial in COVID-19 is ongoing.

Meanwhile a Phase 1 study in GvHD, which was published in prestigious journal Nature Medicine, is probably the closest to commercialisation according to Dr Macdonald.

GvHD is a challenging disease which occurs in patients who have had a bone marrow transplant as part of their chemotherapy treatment for cancer.

Chemo is still very much a sledgehammer therapy where you use very toxic drugs that do kill the cancer cells, but they also kill the surrounding healthy cells that grow hair and bone marrow.

Unfortunately for many patients, the bone marrow transplant reacts against their body and starts to attack all of the tissues in the body, and its ultimately fatal.

Its a horrible death, destroying the lungs, liver, intestines and the skin, Macdonald explains.

Cynatas MSC therapy has been shown to reset that reaction, so the patient can recover from the GvHD, and also recover from their underlying cancer.

With all these clinical trials concurrently under way, Macdonald believes there is a clear significant upside potential for Cynata, particularly given its small market cap of $70m compared to other similar plays like Mesoblast ($1 billion market cap).

Osteopore (ASX:OSX) focuses in bones and specialises in the production of 3D printed bioresorbable implants that are used in surgical procedures to assist with the natural stages of bone healing.

The 3D bio-printer makes a scaffold that mimics bone, with a patented micro-architecture which traps the patients own stem cells.

Orthocell (ASX:OCC) develops collagen medical devices and cellular therapies for the repair and regeneration of human tendons, bone, nerve and cartilage defects.

Its flagship product, the CelGro, is a naturally derived collagen medical device for tissue repair.

Aroa Biosurgery (ASX:ARX) develops FDA-approved medical devices for wounds and tissue repair using its extracellular matrix (ECM) technology, mainly in the United States.

Recent study shows 100% success rates from the use of its Myriad product when patients underwent surgical reconstruction of exposed vital structures such as bone and tendon.

Regeneus (ASX:RGS) Progenza is a cellular therapy targeting pain and inflammation which uses Secretome to improve not only the resident tissue, but the MSCs themselves.

It fills a gap in the current treatment market for osteoarthritis, by providing disease modification and pain relief to address patient symptoms.

Anteris Technologies (ASX:AVR) claims that its Adapt Technology is the first and only bio-scaffold technology that completely re-engineers xenograft tissue into a pure collagen scaffold.

A recent study indicated that Adapt-treated tissue has superior anti-calcification attributes compared with tissues used in competitor valves.

Get the latest Stockhead news delivered free to your inbox.

It's free. Unsubscribe whenever you want.

You might be interested in

Link:
Mesoblast has long been the one poster child for stem cell therapy. Now Cynata and other ASX stocks have e ... - Stockhead

Skin Stem Cells Comments Off on Mesoblast has long been the one poster child for stem cell therapy. Now Cynata and other ASX stocks have e … – Stockhead | December 10th, 2021

Inbreeding and wild tigers at risk of extinction

As habitat fragmentation increases worldwide, wild animal populations are shrinking and becoming more isolated, thus facing a heightened risk of inbreeding and extinction. The extent to which the viability of small, isolated populations could be improved by purging deleterious alleles through natural selection is unclear. Anubhab Khan et al. analyzed whole-genome sequences from 57 wild Bengal tigers from either a small, isolated population or large, connected populations in India. The results revealed evidence of partial purging of highly detrimental variants across populations. However, the small, isolated population showed genomic signs of greater inbreeding and a higher overall frequency of deleterious alleles, compared with two large populations. On average, pairs of individuals from the small, isolated population shared approximately 40% of their genomes in tracts at least 1 megabase long, whereas pairs from the large, connected populations shared approximately 1525% of their genomes. Together, the findings suggest that purging may not eliminate all detrimental alleles and inbreeding-associated fitness costs in small, isolated populations. According to the authors, the findings highlight the need for genetic rescue strategies that enhance the fitness of inbred populations by decreasing the frequency of harmful mutations and increasing genetic variation. J.W.

Read online

Go here to read the rest:
In This Issue - pnas.org

Skin Stem Cells Comments Off on In This Issue – pnas.org | December 10th, 2021

Event summary produced by The Globe and Mail Events team. The Globes editorial department was not involved.

Canada was a pioneer of stem cell research and today, innovators are developing clinical trials to test regenerative treatments for a range of illnesses including cardiac disease and Parkinsons. At the same time, theyre navigating risks and considerations that often surround medical innovations.

The Globe and Mail hosted a webcast on November 30 to explore the promise and potential of stem cells. Speakers also discussed ethical issues, misinformation and the importance of rigorous evaluation in bringing new treatments to market.

Missed the live event or would like to view it again? Scroll down to the video player, below.

Andr Picard, health reporter and columnist with The Globe and Mail moderated the event and hosted the following speakers:

Read a summary of the event here

View the full webcast, below:

The Globe and Mail presented the webcast with sponsor support from Bayer.

Go here to see the original:
Stem cells and the future of health care - The Globe and Mail

Cardiac Stem Cells Comments Off on Stem cells and the future of health care – The Globe and Mail | December 10th, 2021

All articles published by MDPI are made immediately available worldwide under an open access license. No specialpermission is required to reuse all or part of the article published by MDPI, including figures and tables. Forarticles published under an open access Creative Common CC BY license, any part of the article may be reused withoutpermission provided that the original article is clearly cited.

Feature Papers represent the most advanced research with significant potential for high impact in the field. FeaturePapers are submitted upon individual invitation or recommendation by the scientific editors and undergo peer reviewprior to publication.

The Feature Paper can be either an original research article, a substantial novel research study that often involvesseveral techniques or approaches, or a comprehensive review paper with concise and precise updates on the latestprogress in the field that systematically reviews the most exciting advances in scientific literature. This type ofpaper provides an outlook on future directions of research or possible applications.

Editors Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world.Editors select a small number of articles recently published in the journal that they believe will be particularlyinteresting to authors, or important in this field. The aim is to provide a snapshot of some of the most exciting workpublished in the various research areas of the journal.

See the original post here:
Cells | Free Full-Text | Improving Cardiac Reprogramming ...

Cardiac Stem Cells Comments Off on Cells | Free Full-Text | Improving Cardiac Reprogramming … | December 10th, 2021

Findings Continue to Change the Treatment of Blood Cancers

HACKENSACK, N.J., Dec. 9, 2021 /PRNewswire/ -- Researchers from Hackensack Meridian Health John Theurer Cancer Center (JTCC), a part of the Georgetown Lombardi Comprehensive Cancer Center, will present updates on treatment advances in multiple myeloma, lymphoma, leukemia, and bone marrow transplantation at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition, to be held virtually and live at the Georgia World Congress Center in Atlanta from December 11-14, 2021.

"John Theurer Cancer Center is a world leader in the care of people with hematologic malignancies and a pioneer in clinical research related to blood cancers. The acceptance of 47 studies from our investigators demonstrates our expertise in this area and our commitment to improving outcomes not only for our own patients, but people affected by these diseases everywhere," said Andre Goy, MD, MS, chairman and executive director of the John Theurer Cancer Center.

This year's presentations will include a plenary session as the #2 ranked abstract for the entire conference with data that will change the paradigm in the treatment of relapsed aggressive lymphoma for the FIRST TIME in 40 years. Dr. Lori Leslie, MD, director of the Indolent Lymphoma and Chronic Lymphocytic Leukemia Research Programs at JTCC will be co-presenter of the phase III international ZUMA-7 clinical trial (abstract #2), which compared axicabtagene ciloleucel (axi-cel) CAR T-cell therapy with standard of care (SOC) in patients with relapsed / refractory diffuse large B-cell lymphoma (DLBCL) after initial therapy. For decades the SOC has been high dose therapy followed by autologous stem cell transplant (ASCT) but patients with high risk disease and / or early relapse still do very poorly. Axi-cel is now used to treat DLBCL that have failed two prior regimens of treatment, including standard salvage chemoimmunotherapy (CIT) followed by ASCT.

Story continues

Bringing axi-cel earlier as second line therapy resulted in a 2.5-fold increase in median event-free survival (defined as the time without any cancer progression or any related complications) and doubled the complete response rate (65% vs 32%).

"This study is the first to change the paradigm for relapsed and refractory DLBCL that was established decades ago, demonstrating significant and clinically meaningful improvements in outcome," said Dr. Leslie. "Axi-cel may replace chemoimmunotherapy and autologous stem cell transplantation as the standard of care for people with DLBCL that relapses or persists after initial treatment. It is a game-changer."

The JTCC presentations address new developments in the treatment of multiple myeloma, lymphoma, leukemia, and bone marrow transplantation, as well as a study assessing gene therapy for sickle cell disease in pediatric patients.

Multiple Myeloma Research

Adding a PI3K inhibitor improved duration of CAR T-cell response. (Abstract #548, David S. Siegel, MD, PhD) In this phase I clinical trial, researchers showed that adding a PI3 kinase inhibitor called bb007 to bb2121 CAR T-cell therapy (forming a combined therapy called bb21217) in relapsed/refractory multiple myeloma (MM) patients who had three or more regimens of treatment resulted in a duration of response of 17 months (compared with 10 months for bb2121 alone in a prior study), and CAR T cells were detectable longer.

Study shows feasibility of "off the shelf" donated CAR T cells. (Abstract #651, David S. Siegel, MD, PhD). Current CAR T-cell therapies involve expensive modification of a patient's own T cells. Allogeneic (donated) CAR T cells represent a potentially more accessible, less expensive option but carry the risk of rejection and complications such as graft-vs-host disease. The phase I UNIVERSAL study demonstrated the safety of donated anti-BCMA CAR T cells in heavily pretreated MM patients, with mild to moderate side effects as expected for this type of immunotherapy.

Novel targeted MM therapies. Three abstracts provided additional data on novel targeted agents for relapsed/refractory MM. Selinexor was FDA approved in December 2020 and is being assessed in combination with other agents. A study of once-weekly oral selinexor with pomalidomide and dexamethasone (abstract #2748, Noa Biran, MD) showed an overall response rate of more than 60% in relapsed/refractory MM, including patients whose disease persisted after CAR T-cell therapy or after anti-CD38 antibody treatment. This is important because patients with MM after CAR T-cell therapy usually do not respond to additional treatment.

Study shows patients fare better if treated in high-volume academic medical centers. (Abstract #2996, David Vesole, MD, PhD, with Lombardi Comprehensive Cancer Center researchers) An analysis of data from the National Cancer Database of nearly 175,000 patients with MM treated at all types of facilities showed that the median overall survival was 75.5 months at high-volume centers versus 50.2 months at low-volume centers. Academic/research cancer programs with high volumes have the best outcomes in MM and are more likely to use chemotherapy, immunotherapy, and autologous stem cell transplantation than low-volume centers, particularly community cancer centers.

Lymphoma Research

Long-term data confirm durability of CAR T-cell benefit in indolent lymphoma. (Abstract #93, Lori Leslie, MD) An update of the pivotal ZUMA-5 clinical trial, which led to the approval of axi-cel CAR T-cell therapy for relapsed/refractory follicular lymphoma, confirmed continued benefit in patients with indolent lymphoma. In follicular lymphoma (most common subtype of indolent lymphoma), high response rates translated to durable responses, with a median duration of response of 38.6 months and 57% of patients free of cancer progression at last follow-up.

Study confirms benefit of CAR T-cell therapy for mantle cell lymphoma (MCL). (Abstract #744, Andre Goy, MD) ZUMA-2 led to the first approval of CAR T-cell therapy for MCL. An analysis of real-world data of MCL patients who received this treatment, 73% of whom would not have been eligible for ZUMA-2, demonstrated similar effectiveness, with an overall response rate of 86% and 64% achieving a complete response. The results support the paradigm-shifting benefit of this therapy in a heavily pretreated patient population where the median overall survival would have otherwise been very poor.

Molecular biomarkers predictive of CAR T-cell response. (Abstract #165, Andrew Ip, MD, Andre Goy, MD) Researchers performed whole exome and transcriptome sequencing to show that patients with DLBCL who had genetic signatures of high-risk disease with standard initial therapy do well with CAR T-cell therapy. Some mutations predicted good versus poor outcomes after CAR T-cell therapyreflecting differences in the tumor or its microenvironmentand may provide the rationale for choosing the most appropriate treatment for each patient and augmenting the response to CAR T-cell therapy.

Value of adding brentuximab to standard chemotherapy for peripheral T-cell lymphoma (Abstract #133, Tatyana Feldman, MD, Lori Leslie, MD) Non-anaplastic subtypes of T-cell lymphoma have poor outcomes and require new options. This study showed that adding brentuximab to conventional combination chemotherapy was tolerable and effective in patients with non-anaplastic CD30-positive peripheral T-cell lymphoma.

Machine learning useful for stratifying lymphoma patients. (Abstract #2395, Andre Goy, MD) Using machine learning and data on 380 patients with DLBCL with expression levels of 180 genes, researchers used machine learning to develop a model to reliably stratify patients with DLBCL treated with R-CHOP combination therapy into four survival subgroups. The model can be used to identify which patients may not respond well to R-CHOPa standard DLBCL treatmentand instead be considered for other therapies or clinical trials.

Lymphoma/CLL adversely affects COVID-19 outcomes. (Abstract #184, Lori Leslie, MD) A study of electronic medical record data on 500 patients with lymphoma, chronic lymphocytic leukemia (CLL), or other lymphoid cancers who tested positive for SARS-CoV-2 showed that those with aggressive non-Hodgkin lymphoma and CLL and patients who had received recent cytotoxic chemotherapy or anti-CD20 antibody treatment (such as rituximab) may be at risk for poor COVID-19 outcomes. JTCC researchers are now working with investigators in the Center for Discovery and Innovation to study T-cell immunity in people with cancer.

Other studies focused on adding ublituximab and umbralisib to ibrutinib in people with CLL (Abstract #395, Lori Leslie, MD) and assessing cerdulatinib as monotherapy for patients with relapsed/refractory peripheral T-cell lymphoma (Abstract #622, Tatayana Feldman, MD).

Leukemia Research

Oral therapy for low-risk myelodysplastic syndrome (MDS) (Abstract #66, James McCloskey, MD) People with MDS are at risk for developing acute leukemia. Those with low-risk MDS may receive supportive care for low blood counts. Patients with high-risk MDS have received inconvenient injections with drugs such as azacitidine and decitabine. This study showed that oral decitabine and cedazuridine was pharmacokinetically equivalent to intravenous decitabine; in patients with low-risk MDS, the oral treatment was well tolerated with prolonged treatment and may be useful for preventing the progression of this disease to leukemia.

Effectiveness of adding venetoclax to gilteritinib effective for FLT3-mutated acute leukemia (Abstract #691, James McCloskey, MD) Acute myeloid leukemia (AML) with FLT3 mutations initially responds to FLT3 inhibitors but frequently becomes resistant to these drugs. This study showed that giving venetoclax (a BCL2 inhibitor) with the FLT3 inhibitor gilteritinib was very effective, clearing the FLT3 mutation in most patients, and was associated with longer overall survivaleven in patients with high-risk subtypes.

Liquid biopsy for detecting molecular abnormalities in AML (Abstract #3463, Jamie Koprivnikar, MD, James McCloskey, MD, and others) This study assessed next-generation sequencing (NGS) to detect molecular abnormalities in AML using liquid biopsies. The data show that this approach is reliable for detecting structural chromosomal abnormalities in myeloid neoplasms. It could potentially replace the need for conventional cytogenetic testing, be much more convenient (replacing bone marrow biopsies for materials), and be more cost-effective.

Bone Marrow Transplantation Research

Next-generation sequencing and liquid biopsy valuable for detecting early relapse after stem cell transplantation. (Abstract #1828, Scott Rowley, MD, Michele Donato, MD, Maher Albitar, MD, and others) Cell-free DNA was isolated from the peripheral blood post-allogeneic transplant in patients treated for AML, acute lymphocytic leukemia, chronic myelogenous leukemia, chronic myelomonocytic leukemia, MDS, MM, and lymphoma. Researchers showed that NGS and liquid biopsy are useful for detecting residual disease. The data suggest that this approach, which examines cancer DNA in peripheral blood rather than a sample from a bone marrow biopsy, may be effective for detecting and managing minimal residual disease (MRD)the next frontier in oncologyenabling doctors to modify therapy to achieve MRD negative status or, during transplantation, to adjust immunosuppressors or use additional T cells to prevent relapse.

Use of NGS and machine learning after transplant to predict graft-vs-host disease (GVHD) (Abstract #2892, Scott Rowley, MD, Michele Donato, MD, Maher Albitar, MD, and others) Using NGS RNA sequencing plus a machine learning approach, researchers looked at over 1,400 genes in 46 patients who had an allogeneic bone marrow transplant and developed a model based on 7 genes to predict acute GVHD, one of the most significant complications of receiving a transplant from a bone marrow donor. There are currently no valid ways to predict acute GVHD and intervene early until patients become symptomatic. The ability to identify molecular markers of this complication while patients are asymptomatic may allow for early intervention to prevent GVHD.

Sickle Cell Disease Research

Sustained quality of life in patients receiving gene therapy for sickle cell disease (Abstract #7, Stacey Rifkin-Zenenberg, DO, Hackensack University Medical Center) LentiGlobin gene therapy (bb1111) has been under study in a clinical trial as a one-time treatment and cure for sickle cell disease. This study presented long-term quality of life data for one group in the study, demonstrating an improvement in hematologic parameters and complete resolution of veno-occlusive events and related pain as well as sustained and clinically meaningful improvement in quality of life 6 and 24 months post-treatment. Even patients with the worst baseline quality of life scores experienced a benefit. LentiGlobin is the first gene therapy for sickle cell disease and the results of this study are very promising, with the potential to change patient outcomes for this chronic debilitating disease.

The full set of ASH data presentations by JTCC researchers is as follows:

Abstract #

Type

Title

Authors

Presenting (PST)

2

Plenary Scientific Session

Primary Analysis of ZUMA-7: A Phase 3 Randomized Trial of Axicabtagene Ciloleucel (Axi-Cel) Versus Standard-of-Care Therapy in Patients with Relapsed/Refractory Large B-Cell Lymphoma

Lori A. Leslie

Sunday, December 12, 2021: 2:00 PM-4:00 PM

7

Oral

Sustained Improvements in Patient-Reported Quality of Life up to 24 Months Post-Treatment with LentiGlobin for Sickle Cell Disease (bb1111) Gene Therapy

Stacey Rifkin

Saturday, December 11, 2021: 9:30 AM-11:00 AM

50

Oral

A Large Multicenter Real-World Evidence (RWE) Analysis of Autoimmune (AI) Diseases and Lymphoma: Histologic Associations, Disease Characteristics, Survival, and Prognostication

Tatyana A. Feldman, Jason Lofters

Saturday, December 11, 2021: 9:45 AM

66

Oral

Oral Decitabine/Cedazuridine in Patients with Lower Risk Myelodysplastic Syndrome: A Longer-Term Follow-up of from the Ascertain Study

James K McCloskey

Saturday, December 11, 2021: 10:45 AM

93

Oral

Long-Term Follow-up Analysis of ZUMA-5: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory (R/R) Indolent Non-Hodgkin Lymphoma (iNHL)

Pashna N. Munshi, Lori A. Leslie,

Saturday, December 11, 2021: 10:00 AM

133

Oral

Brentuximab Vedotin Plus Cyclophosphamide, Doxorubicin, Etoposide, and Prednisone (CHEP-BV) Followed By BV Consolidation in Patients with CD30-Expressing Peripheral T-Cell Lymphomas

Tatyana A. Feldman, Lori A. Leslie

Saturday, December 11, 2021: 12:00 PM-1:30 PM

165

Oral

Impact of Molecular Features of Diffuse Large B-Cell Lymphoma on Treatment Outcomes with Anti-CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy

Andrew Ip, MD, Andre Goy

Saturday, December 11, 2021: 12:30 PM

184

Oral

A Multi-Center Retrospective Review of COVID-19 Outcomes in Patients with Lymphoid Malignancy

Lori A. Leslie

Saturday, December 11, 2021: 12:00 PM-1:30 PM

307

Oral

Post Hoc Analysis of Responses to Ponatinib in Patients with Chronic-Phase Chronic Myeloid Leukemia (CP-CML) By Baseline BCR-ABL1 Level and Baseline Mutation Status in the Optic Trial

James K McCloskey

Saturday, December 11, 2021: 4:00 PM-5:30 PM

395

Oral

A Phase 2 Study Evaluating the Addition of Ublituximab and Umbralisib (U2) to Ibrutinib in Patients with Chronic Lymphocytic Leukemia (CLL): A Minimal Residual Disease (MRD)-Driven, Time-Limited Approach

Lori A. Leslie

Sunday, December 12, 2021: 10:30 AM

548

Oral

Updated Clinical and Correlative Results from the Phase I CRB-402 Study of the BCMA-Targeted CAR T Cell Therapy bb21217 in Patients with Relapsed and Refractory Multiple Myeloma

David S. Siegel

Sunday, December 12, 2021: 4:30 PM-6:00 PM

561

Oral

Polyclonality Strongly Correlates with Biological Outcomes and Is Significantly Increased Following Improvements to the Phase 1/2 HGB-206 Protocol and Manufacturing of LentiGlobin for Sickle Cell Disease (SCD; bb1111) Gene Therapy (GT)

Stacey Rifkin-Zenenberg

Sunday, December 12, 2021: 4:30 PM-6:00 PM

622

Oral

Phase 2a Study of the Dual SYK/JAK Inhibitor Cerdulatinib (ALXN2075) As Monotherapy in Patients with Relapsed/Refractory Peripheral T-Cell Lymphoma

Feldman

More:
John Theurer Cancer Center Investigators Present Pioneering Research at the American Society of Hematology Annual Conference - Yahoo Finance

Cardiac Stem Cells Comments Off on John Theurer Cancer Center Investigators Present Pioneering Research at the American Society of Hematology Annual Conference – Yahoo Finance | December 10th, 2021

LAWRENCE The human body contains trillions of cells at any given moment, each doing highly specialized work to help us function but they dont operate in isolation. Imagine a sophisticated FedEx or UPS delivery network empowering communication between our cells. The nano-sized delivery vehicles in this scenario are called exosomes, and a company born from technology developed at the University of Kansas is harnessing the power of these tiny vessels to enable tomorrows medical breakthroughs.

Clara Biotech, founded by KU engineering alumnus Jim West and former KU professor of chemical & petroleum engineering and chemistry Mei He, has spent the last three years refining a novel technology to isolate and purify exosomes, which can be used for early disease diagnosis, targeted drug delivery, cancer immunotherapy and other forms of regenerative medicine.

Now, the company is poised to commercialize its first product after recently finalizing $1.5 million in seed funding and being recognized in a national competition. Clara Biotech was the only Midwest company singled out in MedTech Innovators Biotools Innovator program, which recognizes the 10 best life science tools startups. The company received $10,000 for securing a spot in the 2021 cohort and a $5,000 best-video award for a one-minute spot introducing the company and detailing what sets it apart.

Clara Biotech was founded to help move exosomes from the bench to the bedside, said West, who serves as Claras CEO. Our company is about building a platform that everybody can leverage to bring their products to market and help solve challenges around isolation and purification, which today is one of the number one issues in the field.

Exosomes deliver genetic information to cells throughout the body. Exosomes from regenerative cells, such as stem cells, can help the body heal and repair itself. Exosomes released from diseased cells might be used for early detection and diagnosis of cancer and other conditions.

But at 100 nanometers in diameter less than the wavelength of visible light exosomes are difficult to handle.

Clara Biotechs patented ExoRelease platform is unique in the industry. Current processes rely on bulk isolation, whereas Claras capture and release technology isolates pure exosomes. This allows researchers to easily isolate and target specific exosomes including cardiac, neurological, cancer and others and use them for therapeutic treatments and drug delivery platforms.

Im very excited about the work that Clara Biotech is doing to improve exosome purification, said Kathryn Zavala, managing director of BioTools Innovator. Their technology has the potential to significantly impact how we diagnose and treat diseases by advancing the field of exosome research and development.

Clara Biotech launched in 2018 with a Small Business Innovation Research grant from the National Cancer Institute and received training through the National Science Foundations Innovation Corps (I-Corps) program on how to transfer knowledge into products and processes that benefit society. It has seven full-time employees, and its lab is housed in the KU Innovation Park.

Clara Biotech is an example of how KU innovation provides the foundation to form a company that addresses societal needs and creates Kansas jobs, said Tricia Bergman, KUs director of strategic partnerships. It also illustrates how technology developed in KU labs can transition into the KU Innovation Park, where the company can continue to develop through ongoing partnerships with the university.

Until now, Clara Biotech has provided lab services to its customers. Now, its moving toward packaging its technology so other companies, labs and researchers can leverage it to complete the isolation process themselves.

Were trying to democratize access to these exosomes, West said.

Clara Biotech is beta-testing kits containing its isolation technology with promising results from early adopters and hopes to launch its first product by the end of the year.

Building a company is probably the hardest thing Ive ever done in my life, but its also super rewarding, West said. The work were doing is really important.

Photo: Jim West, CEO of Clara Biotech, holds the two checks his company won at MedTech Innovators Biotools Innovator program in San Diego in October.

Read the original:
Biotech company with KU roots wins national competition, secures funding to help move research 'from bench to bedside' | The University of Kansas - KU...

Cardiac Stem Cells Comments Off on Biotech company with KU roots wins national competition, secures funding to help move research ‘from bench to bedside’ | The University of Kansas – KU… | December 10th, 2021

BURLINGTON, Mass.--(BUSINESS WIRE)--PharmaEssentia USA Corporation, a subsidiary of PharmaEssentia Corporation (TPEx:6446), a global biopharmaceutical innovator based in Taiwan leveraging deep expertise and proven scientific principles to deliver new biologics in hematology and oncology, today announced that BESREMi (ropeginterferon alfa-2b-njft) is now commercially available in the U.S. to eligible patients with polycythemia vera (PV). BESREMi was approved by the FDA in November as the only interferon for adults with polycythemia vera. BESREMi was approved with a boxed warning for risk of serious disorders including aggravation of neuropsychiatric, autoimmune, ischemic and infectious disorders.

Today marks the beginning of a new chapter in the treatment of PV. Our team is delivering on our goal to bring an innovative solution that may help more people manage not only the symptoms of PV, but target the disease itself to gain durable control with potential to reduce progression over time, said Meredith Manning, U.S. General Manager. We look forward to working closely with U.S. providers to raise awareness of this therapy and help advance treatment goals.

PharmaEssentia SOURCE Now Available to Support People with PV in the U.S.

With the commercial availability of BESREMi, PharmaEssentia is also launching a comprehensive patient support program, which can be found at http://www.pharmaessentiaSOURCE.com.

The SOURCE program is available for patients prescribed BESREMi and offers a full suite of services designed to help patients start and stay on therapy. Services include insurance navigation support, titration and injection training, and ongoing adherence guidance. The program also includes physician resources, including guides to help patients get started on treatment and ordering processes.

As part of this program, PharmaEssentia will help patients with financial barriers to starting therapy. The company is offering co-pay and co-insurance programs to assist eligible patients who experience financial need. Programs include a $0 copay card for commercially insured patients, temporary product supply in case of insurance delays and/or gaps in coverage, free drug for the uninsured and under-insured as well as assistance identifying additional support as needed.

Weve designed SOURCE with active input from the PV community to simplify the process for appropriate patients to initiate and maintain access to BESREMi and to benefit from its effects over the long-term, added Manning. Our goal is to ensure that any appropriate person with PV who is prescribed BESREMi is able to receive the therapy.

About Polycythemia Vera

Polycythemia Vera (PV) is a cancer originating from a disease-initiating stem cell in the bone marrow resulting in a chronic increase of red blood cells, white blood cells, and platelets. PV may result in cardiovascular complications such as thrombosis and embolism, and often transforms to secondary myelofibrosis or leukemia. While the molecular mechanism underlying PV is still subject of intense research, current results point to a set of acquired mutations, the most important being a mutant form of JAK2.1

About BESREMi

BESREMi is an innovative monopegylated, long-acting interferon. With its unique pegylation technology, BESREMi has a long duration of activity in the body and is aimed to be administered once every two weeks (or every four weeks with hematological stability for at least one year), allowing flexible dosing that helps meet the individual needs of patients. After one year, patients with stable complete hematologic response (CHR) can be treated with BESREMi every four weeks.

BESREMi has orphan drug designation for treatment of PV in the United States. The product was approved by the European Medicines Agency (EMA) in 2019 and has received approval in Taiwan and South Korea. BESREMi was invented and is manufactured by PharmaEssentia.

Important Safety Information

IMPORTANT SAFETY INFORMATION AND INDICATIONS

WARNING: RISK OF SERIOUS DISORDERS

Interferon alfa products may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping therapy.

CONTRAINDICATIONS

WARNINGS AND PRECAUTIONS

Other central nervous system effects, including suicidal ideation, attempted suicide, aggression, bipolar disorder, mania and confusion have been observed with other interferon alfa products.

Closely monitor patients for any symptoms of psychiatric disorders and consider psychiatric consultation and treatment if such symptoms emerge. If psychiatric symptoms worsen, it is recommended to discontinue BESREMi therapy.

ADVERSE REACTIONS

The most common adverse reactions reported in > 40% of patients in the PEGINVERA study (n=51) were influenza-like illness, arthralgia, fatigue, pruritis, nasopharyngitis, and musculoskeletal pain. In the pooled safety population (n=178), the most common adverse reactions greater than 10%, were liver enzyme elevations (20%), leukopenia (20%), thrombocytopenia (19%), arthralgia (13%), fatigue (12%), myalgia (11%), and influenza-like illness (11%).

DRUG INTERACTIONS

Patients on BESREMi who are receiving concomitant drugs which are CYP450 substrates with a narrow therapeutic index should be monitored to inform the need for dosage modification for these concomitant drugs. Avoid use with myelosuppressive agents and monitor patients receiving the combination for effects of excessive myelosuppression. Avoid use with narcotics, hypnotics or sedatives and monitor patients receiving the combination for effects of excessive CNS toxicity.

USE IN SPECIFIC POPULATIONS

Please see accompanying full Prescribing Information, including Boxed Warning.

About PharmaEssentia

PharmaEssentia Corporation (TPEx: 6446), based in Taipei, Taiwan, is a rapidly growing biopharmaceutical innovator. Leveraging deep expertise and proven scientific principles, the company aims to deliver effective new biologics for challenging diseases in the areas of hematology and oncology, with one approved product and a diversifying pipeline. Founded in 2003 by a team of Taiwanese-American executives and renowned scientists from U.S. biotechnology and pharmaceutical companies, today the company is expanding its global presence with operations in the U.S., Japan, China, and Korea, along with a world-class biologics production facility in Taichung. For more information, visit our website or find us on LinkedIn and Twitter.

Forward Looking Statement

This press release contains forward looking statements, including statements regarding the timing of BESREMis availability in the United States, the commercialization plans and expectations for commercializing BESREMi in the United States, and the potential benefits or competitive position of BESREMi. For those statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995 and similar legislation and regulations under Taiwanese law. These forward-looking statements are based on management expectations and assumptions as of the date of this press release, and actual results may differ materially from those in these forward-looking statements as a result of various factors. These factors include PharmaEssentias ability to launch BESREMi in the United States, whether BESREMi is successfully commercialized and adopted by physicians and patients, the extent to which reimbursement is available for BESREMi, and the ability to receive FDA and other regulatory approvals for additional indications for BESREMi. Any forward-looking statements set forth in this press release speak only as of the date of this press release. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. The information found on our website, and the FDA website, is not incorporated by reference into this press release and is included for reference purposes only.

1 Cerquozzi S, Tefferi A. Blast Transformation and Fibrotic Progression in Polycythemia Vera and Essential Thrombocythemia: A Literature Review of Incidence and Risk Factors. Blood Cancer Journal (2015) 5, e366; doi:10.1038/bcj.2015.95.

2021 PharmaEssentia Corporation. All rights reserved. US-BSRM-2100225 11/21

BESREMi and PharmaEssentia are registered trademarks of PharmaEssentia Corporation, and the PharmaEssentia logo and PharmaEssentia SOURCE are trademarks of PharmaEssentia Corporation.

More here:
PharmaEssentia's BESREMi (ropeginterferon alfa-2b-njft) Now Available for the Treatment of People With Polycythemia Vera in the United States -...

Cardiac Stem Cells Comments Off on PharmaEssentia’s BESREMi (ropeginterferon alfa-2b-njft) Now Available for the Treatment of People With Polycythemia Vera in the United States -… | December 10th, 2021

On International Day of Disabled Persons, TheHealthSite spoke to Dr. Sunil Bhat, Director and Clinical Lead, Pediatric Hematology, Oncology, and Blood & Marrow Transplantation, Mazumdar Shaw Cancer Centre, Narayana Health City, to discuss the condition and understand the ways one can manage it.

Written by Satata Karmakar | Updated : December 3, 2021 5:31 PM IST

3rd December every year is observed as UN-designated International Day for persons with disabilities. The observance of the Day aims to promote an understanding of disability issues and mobilize support for the dignity, rights, and well-being of persons with disabilities. This year's theme is "not all disabilities are visible" since some of the disabilities are non-visible but they cause significant challenges for people living with such conditions for day-to-day participation in society.

Such non-visible disabilities include some of the rare blood disorders such as Thalassemia, Aplastic Anemia, Sickle cell Anemia, Fanconi Anemia, Hemophilia, and so on. The Rights of People with Disability Bill passed by the Parliament of India in December 2016 included newer disabilities like blood disorders sickle cell anemia, thalassemia, and hemophilia. Today, on International Day of Disabled Persons, TheHealthSite spoke to Dr. Sunil Bhat, Director and Clinical Lead, Pediatric Hematology, Oncology, and Blood & Marrow Transplantation, Mazumdar Shaw Cancer Centre, Narayana Health City, to discuss the condition and understand the ways one can manage it.

In India, the burden of blood disorders and blood cancer is huge. India is even called as Thalassemia capital of the world with over 10,000 new cases every year. Thalassemia is a disabling condition not just because of chronic anemia but other co-morbidities like organ damage, bone damage, and cardiac complications.

People with thalassemia may need lifelong blood transfusions and other therapies (like iron removal medications). With the advances in the medical field, blood stem cell transplant plays an important role in the treatment of various blood disorders like thalassemia, aplastic anemia, and blood cancers as well. For a blood stem cell transplant to be deemed successful, the human leukocyte antigens (HLA) of the donor should match the antigens present in the cells of the patient. Only 30% of the patients find a matching donor in the family and the rest 70% depending on an unrelated donor. Such unrelated donors are being registered by stem cell registries like DKMS BMST Foundation India.

However, despite such a huge disease burden, Indian stem cell donors only form a tiny fraction, about 0.04% of the total listed unrelated donors globally. The main reason is the lack of awareness and prevailing myths around the stem cell donation process deny many patients a second chance at their lives in the country. It is high time that healthy people understand blood stem cell donation is a safe process and come forward to register as a donor. There is only a 1 in a million chance that someone comes as a match for a patient!

Follow us on

Read more here:
Rare Blood Disorders In India: How It Can Lead To Disabilities In People Expert Explains | TheHealthSite. - TheHealthSite

Cardiac Stem Cells Comments Off on Rare Blood Disorders In India: How It Can Lead To Disabilities In People Expert Explains | TheHealthSite. – TheHealthSite | December 10th, 2021

Shahid Akhter, editor, ETHealthworld, spoke to Ramesh Ramadurai, MD, 3M India, to know more 3M collaborations that can improve and impact cancer care, besides cutting down on the costs in a big way.

How has the technological and infrastructural facilities impacted Bone Marrow Transplantation in India ?Every year nearly 20,000 Indian patients, including many children, who suffer from blood and solid cancers require bone marrow transplantation (BMT). However, only 2,000 of these patients are fortunate enough to receive this therapy, as the cost of bone marrow transplantation can vary from INR 10 Lakhs to 30 Lakhs. It is imperative to reduce the cost of cancer treatment while maintaining a stringent focus on sterilization and quality. It is indeed the need of the hour for us to address this issue.

What are the various technological advancement required for the better functioning of the facilities?Despite the increasing demand for bone marrow transplantation, the number of bone marrow doners in India is astonishingly low. India conducts stem cell transplant procedure for approximately 2,000 every year, while around 80,000 to 100,000 annual transplants are required to tackle the burden of blood cancers and fatal blood disorders. Finding a matching donor is very difficult. This option is exercised only after the alternative options have failed.

India has only about 400,000 donors registered on the bone marrow registry. Chances of finding a donor match are as low as 10% to 15% compared to the West where the chances of matching are as high as 60% to 70% due to higher rates of donations.

What are the major and significant developments in treating bone marrow cancer in the country?A bone marrow registry collects information on individuals willing and able to donate bone marrow and gathers the donor information into a database. In India, organisations like Datri are helping to create a pool of donors to help people who do not have blood-related donors by finding an unrelated match for life-saving treatment.

Infusion of a memory cell is another advancement. This involves taking out the cells, sorting the good cells and the memory cells or the fighting cells, which can fight infections, sorting them out, capturing them and putting them back into the body after giving the requisite chemotherapy. This is also called T-cell depletion with memory cell infusion. It is now available in India and is affordable.

Through this partnership with United Way Bengaluru and Sri Shankara Cancer Hospital and Research Centre (SSCHRC), how does 3M aim to foster accessibility for people from different sections of the society in treating cancer. 3M India was brought into the SSCHRC family through United Way of Bengaluru, and this is our second round of engagement with the hospital. Last year, 3M India had donated equipment for cancer research and diagnostics like the Sanger sequencer and QPCR, made enhancements to the childrens play area at the long-stay Lakshmi Childrens center with child-friendly wall graphics, and provided kitchen utensils and cooking counters for the resident families of paediatric cancer patients.

We have donated several critical equipments for the research labs which contribute to the successful treatment of the BMT patients. As on date the BMT unit at SSCHRC has treated and discharged 5 patients and currently 4 are undergoing treatment. This wing of the hospital is accessible by few staff nurses and specialists like Dr K N Nataraj who is the Chief of Adult and Paediatric Haematology at the hospital. For a successful bone marrow transplantation, there are several requisites, some of which include, successful donor matching, extremely technique-sensitive harvesting and transplantation processes and robust infection control. With this essential, life-saving equipment, the cost of the treatment will reduce to approximately 50% (between Rs 8-12 Lacs as against the actual cost of Rs 15- 30 lacs) and help the hospital treat many more cancer patients.

How do 3M India and Sri Shankara Hospital plan to take this initiative ahead in the future for the growth and enhancement of bone marrow transplantation in the facility? It is matter of pride for 3M India and United Way of Bengaluru that we are associated with SSCHRC, an institution at the forefront of providing comprehensive cancer treatment to the needy, through CSR interventions.

By complying with the Foundation for the Accreditation of Cellular Therapy (FACT) Guidelines, the BMT Centre will be a one-of-a-kind medical facility where people of all economic status can receive treatment. Being a growing facility, the hospital is committed to continuing its responsibility towards expansion of multiple hospital beds and medical care. We are inspired by the commitment of the doctors and Sri Shankara Board of Trustees, led by Dr. B.S. Srinath and other dedicated professionals who developed a multifaceted approach to establishment a state of the art, affordable cancer hospital that is accessible to all irrespective of caste, creed, religion, gender or socioeconomic status.

More:
It is imperative to reduce the cost of cancer treatment: Ramesh Ramadurai, MD, 3M India - ETHealthworld.com

Cardiac Stem Cells Comments Off on It is imperative to reduce the cost of cancer treatment: Ramesh Ramadurai, MD, 3M India – ETHealthworld.com | December 10th, 2021

Las Vegas, USAPolymyositis Pipeline to Progress with New and Emerging Drugs for Treatment, Analyzes , Dec. 08, 2021 (GLOBE NEWSWIRE) -- DelveInsights Polymyositis Pipeline Insight 2021 report offers exhaustive global coverage of available, marketed, and pipeline therapies in different phases of clinical development, major pharmaceutical companies working to advance the pipeline space, and future growth potential of the Polymyositis pipeline domain.

Some of the essential takeaways from thePolymyositis Pipelinereport:

Request a sample and discover more about the report offerings @ Polymyositis Emerging Therapies

The Polymyositis pipeline report lays down detailed profiles of the pipeline assets, comparative analysis of clinical and non-clinical stage Polymyositis products, inactive and dormant assets, comprehensive assessment of driving and restraining factors, as well as the opportunities and risks in the Polymyositis pipeline landscape.

Polymyositis Overview

Polymyositis is a type of inflammatory myopathy, which refers to a group of muscle diseases characterized by chronic muscle inflammation and weakness. Polymyositis (PM), an autoimmune disorder, develops due to abnormal activation of cytotoxic T lymphocytes (CD8 cells) and macrophages against muscular antigens as well as the strong extrafusal muscular expression of major histocompatibility complex 1 causing damage to the endomysium of skeletal muscles. Polymyositis develops gradually over time, and it rarely affects persons younger than age 18.

Find out more about the disease and recent developments @Polymyositis Pipeline Assessment

Polymyositis Pipeline Drugs

Learn more about the novel and emerging Polymyositis pipeline therapies @ Polymyositis Pipeline Analysis

Polymyositis Therapeutics Assessment

ThePolymyositis Pipelinereport proffers an integral view of the Polymyositis emerging novel therapies segmented by Stage, Product Type, Molecule Type, Mechanism of Action and Route of Administration.

By Product Type

By Stage

By Route of Administration

By Molecule Type

By Mechanism of Action

Scope of the Polymyositis Pipeline Report

Dive deep into rich insights for emerging therapies and assessment, visit @ Polymyositis Emerging Therapies

Table of Contents

For further information on the Polymyositis current pipeline therapeutics, reach out @ Polymyositis Ongoing Clinical Trials

Track and assess a candidates clinical development journey through Actionable Intelligence and Comparative Therapeutic Assessment

Related Reports

Polymyalgia Rheumatica Market

DelveInsights Polymyalgia Rheumatica (PMR)Market Insights, Epidemiology, and Market Forecast2030 report deliver an in-depth understanding of the Polymyalgia Rheumatica (PMR), historical and forecasted epidemiology as well as the market trends, market drivers, market barriers, and key companies involved such as Roche Chugai, Bristol-Myers Squibb, Eli Lilly, and others.

Spinal Cord Injury Market

DelveInsights Spinal Cord InjuryMarket Insights, Epidemiology, and Market Forecast - 2030 report delivers an in-depth understanding of the disease, historical, and forecasted epidemiology as well as the market trends, market drivers, market barriers, and key companies involved such as StemCyte, Lineage Cell Therapeutics, Kringle Pharma, AbbVie, Nipro Corporation, ReNetX Bio, Neurofix, and others.

Sarcopenia Market

DelveInsights SarcopeniaMarket Insights, Epidemiology, and Market Forecast-2030 report delivers an in-depth understanding of the disease, historical, and forecasted epidemiology as well as the market trends, market drivers, market barriers and key companies involved such as Biophytis, Novartis, Eli Lily, Immunoforge, Regeneron Pharmaceuticals, Sanofi, and others.

Thrombocytopenia MarketDelveInsights Thrombocytopenia Market Insights, Epidemiology, and Market Forecast2030 report deliver an in-depth understanding of the Thrombocytopenia, historical and forecasted epidemiology as well as the Thrombocytopenia market trends, market drivers, market barriers, and key companies involved such as Sanofi (Ablynx), Rigel Pharmaceuticals, Kissei Pharmaceutical, UCB Biopharma, Principia Biopharma, and others.

Tendinopathy Market

DelveInsights Tendinopathy-Market Insights, Epidemiology, and Market Forecast2030 report deliver an in-depth understanding of the Tendinopathy, historical and forecasted epidemiology as well as the Tendinopathy market trends, market drivers, market barriers, SWOT analysis, reimbursement, and market access, and key companies involved such as MiMedx Group, R3 Stem Cell, Novartis Pharmaceuticals, University of Wisconsin-Madison, General Electric, Ipsen, Orthocell Limited.

Warm Autoimmune Hemolytic Anemia Market

DelveInsights Warm Autoimmune Hemolytic Anemia Market Insights, Epidemiology, and Market Forecast2030 report deliver an in-depth understanding of the wAIHA, historical and forecasted epidemiology as well as the market trends, market drivers, market barriers, and key companies involved such as Rigel Pharmaceuticals, Apellis Pharmaceuticals, Johnson & Johnson, Immunovant, Alexion Pharmaceuticals, Sanofi, Incyte Corporation, Annexon, and others.

Browse Through Our Blog Posts

AboutDelveInsight

DelveInsight is a leading Business Consultant, and Market Research firm focused exclusively on life sciences. It supports Pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platformPharmDelve.

For more insights, visit Pharma, Healthcare, and Biotech News

Read the rest here:
Polymyositis Pipeline to Progress with New and Emerging Drugs for Treatment, Analyzes DelveInsight - GlobeNewswire

Spinal Cord Stem Cells Comments Off on Polymyositis Pipeline to Progress with New and Emerging Drugs for Treatment, Analyzes DelveInsight – GlobeNewswire | December 10th, 2021