The Seoul National University Hospital (SNUH) said its research team has opened a way to raise bone marrow's success rate drastically.

The team has discovered a special macrophage that allows mass-producing top hematopoietic stem cells (HSCs) for the first time globally. By making the most of this special macrophage, we expect to mass-produce the youngest HSCs that are also most capable of differentiating, it said.

Bone marrow (HSC) transplantation is an important treatment that provides blood cancer patients with a chance to be cured. Medical professionals can also expand the techniques indications to treat blood diseases, such as dysplastic anemia, bone marrow dysplasia syndrome, lymphoma, multiple myeloma, complex immunodeficiency, and autoimmune diseases.

A technique is needed to amplify top HSCs to improve bone marrow transplantations efficiency, but it remains in its infancy. In addition, cells that maintain homeostasis by controlling the dormancy and proliferation of HSCs are also difficult to prove.

A joint research team of Ludwig-Maximilian University in Germany, Queen Mary University in the U.K., and Harvard University in the U.S. has claimed that red blood cells expressing large amounts of the DARC (ACKR1) protein were crucial in maintaining the homeostasis of HSCs, which, however, has failed to be proven objectively.

The SNUH team, led by Professors Kim Hyo-soo and Kwon Yoo-wook, researched key cells and the mechanisms responsible for controlling HSC homeostasis and found a few macrophages expressing triple protein markers (SMA, COX2, DARC) can maintain homeostasis of top HSCs.

When the DARC-Kai1 protein bond is dissolved, hematopoietic stem cells begin to increase, resulting in mass production of blood cells and vice versa when the macrophages DARC protein and the HSCs Kai1 protein combine. Subsequently, if this bonding is controlled, the researchers expect a culture method that mass-produces top HSCs with excellent hematopoietic function can be developed.

This mechanism can also be used to develop treatments for bone marrow dysfunction, such as leukemia and malignant anemia, and increase the success rate of bone marrow transplants.

"If a method is commercialized to mass-produce and store top HSCs while maintaining their youthfulness, it will be possible to develop a customized treatment that can quickly help patients needing a bone marrow transplant," Professor Kim said.

This study was published in the Cell Stem Cell journal.

Visit link:
SNUH team finds a key cell that keeps top hematopoietic stem cells young - KBR

Bone Marrow Stem Cells Comments Off on SNUH team finds a key cell that keeps top hematopoietic stem cells young – KBR | July 16th, 2022

Introduction

Traumatic brain injury is one of the main causes of deaths, disabilities, and hospitalization in the world. In the USA, around 30% of all injury-related deaths are due to traumatic brain injury.1 Globally, traumatic brain injury affects the lives of about 10 million people each year.2 It happened as the brain tissue is damaged by an external force, the result of direct impact, rapid acceleration or deceleration, a piercing object, and blast waves from an explosion.3 Visual impairment, cognitive dysfunction, hearing loss, and mental health disorders are among the most common complications affecting traumatic brain injury patients and their families. The pathophysiology of traumatic brain injury is not clear since the structure of the brain is complex with many cell types such as neurons, astrocytes, oligodendrocytes, microglia, and multiple subtypes of these cells. Traumatic brain injury occurs in two phases. These are primary (acute) and secondary (late) brain injuries. The primary injury is the initial blow to the head; in this phase, brain tissue and cells such as neurons, glial cells, endothelial cells, and the bloodbrain barrier are damaged by mechanical injury. The secondary injury occurs after primary injury and in these late phases, several toxins are released from the injured cells leading to the formation of cytotoxic cascades, which increase the initial brain damage.4 The primary brain injury causes the dysfunction of the bloodbrain barrier and initiates local inflammation and secondary neuronal injury. In addition, severe and long-term inflammation causes severe neurodegenerative and inflammatory diseases. Repairing of tissue damage needs the inhibition of secondary injury and rapid regeneration of injured tissue.5 Depending on the nature of the injury, neurons and neuroglial cells may be damaged; excessive bleeding may happen, axons may be destroyed and a contusion may occur.6 Moreover, the pathogenesis of traumatic brain injury involves bloodbrain barrier damage, neural inflammation, and diffuse neuronal degeneration.7 Unlike other organs, it has long been thought that mature brain tissue cannot be able to repair itself after injury.8 However, the current research indicated that multipotent neural stem/progenitor cells are residing in some areas of the brain throughout the lifespan of an animal, implying the mature brains ability to produce new neurons and neuroglial cells.9 In the previous decades, several studies have shown that the mature neurons in the hippocampal dentate gyrus of the brain play significant roles in hippocampal-induced learning and memory activities,9 while new olfactory interneurons produced from the subventricular zone are essential for the appropriate functioning of the olfactory bulb network and some specific olfactory behaviors.10 After traumatic brain injuries, clinical evidence indicated that endogenous neural progenitor cells might play an important role in regenerative medicine to treat brain injury because an increased neurogenic regeneration ability has been reported in different types of brain injury models of animal and human studies.11 Nowadays, there is a new therapeutic approach for traumatic brain injury that involves the use of stem cells for neural regeneration and restoration. Exogenous stem cell transplantation has been found to accelerate immature neuronal development and increase endogenous cellular proliferation in the damaged brain region.12 A better understanding of the endogenous neural stem cells regenerative ability as well as the effect of exogenous neural stem cells on proliferation and differentiation may help researchers better understand how to increase functional recovery and brain tissue repair following injury. Therefore, in this study, we discussed the therapeutic effects of stem cells in the repair of traumatic brain injury.

Traumatic brain injury causes severe stress on the brain, making it extremely hard to keep appropriate cognitive abilities. Even though many organs in the body, for example, the skin, can regenerate following injury, the brain tissue may not easily repair. In the adult brain, endogenous neural stem cells are primarily localized to the subventricular zone of the lateral ventricles and the subgranular zone of the hippocampal dentate gyrus.13 In the subventricular zone, neural stem/progenitor cells generate neuronal and oligodendroglial progenies.14 Most of the new neurons produced from the subventricular zone migrate via the rostral migratory stream, eventually becoming olfactory interneurons in the olfactory bulb.15 A few subventricular zone-derived new neurons travel into cortical areas for an unknown cause but may be related to tissue repair or renewal mechanisms.16 Similarly, newly produced dentate gyrus cells travel laterally into the dentate granule cell layer and become fully mature in a few weeks through a process known as adult hippocampus neurogenesis.17 However, it is still unknown whether these neural stem cells in the subventricular zone and dentate gyrus regions can replace the lost neurons following injury.

So far, several studies have assessed the degree of neurogenesis in these two areas and have demonstrated that significant numbers of new cells are continuously generated.9,18 For example, the rat dentate gyrus generates about 9000 new cells each day or 270,000 cells every month.18 A current clinical finding indicated that the whole granular cell population in the deep layer and half of the superficial layer of the olfactory bulb were replaced by newly produced mature neurons for a year.19 A similar study also revealed that adult-produced neurons account for around 10% of the overall number of dentate granule cells in the hippocampus and they are uniformly distributed along the anterior-posterior axis of the dentate gyrus.19 After the finding of continuous adult neurogenesis during the lifetime in the adult animal brain, the functional roles and the significance of this adult neurogenesis, mainly hippocampal neurogenesis concerning learning and memory processes, have been widely explored. Previous studies showed factors that increase hippocampal neurogenesis such as exposure to enriched environments, physical activity, or growth factor therapy may improve cognitive abilities.2022

The newly formed granular cells in the mature dentate gyrus can become functional neurons in the normal hippocampus by demonstrating passive membrane characteristics, generating action potentials, and receiving functional synaptic inputs, as seen in the adult dentate gyrus neurons.23 For instance, mouse strains hereditarily having poor levels of neurogenesis carry out low learning activities than those with a higher level of baseline neurogenesis.2325 A variety of physical and chemical signals influence the proliferation and maturational destiny of cells in the subventricular zone and dentate gyrus. For instance, biochemical variables including serotonin, glucocorticoids, ovarian hormones, and growth factors strongly regulate the proliferative response, implying that cell proliferation in these areas has a significant physiological role.26,27 Besides, physical factors such as exercise and stress produce changes in cell proliferation implying a significant role in network adaptation.28,29 For example, physical exercise might cognitively and physically enhance the production of cells and neurogenesis within the subventricular zone and dentate gyrus, but stress inhibits this type of cellular activity. Furthermore, the physiologic role of these new cells depends on the number of cells being produced, survival rate, differentiation ability, and integration of cells into existing neuronal circuity.24,30

The subventricular zone and hippocampus contain neural stem cells that respond to a variety of stimuli. Different kinds of experimental traumatic brain injury models such as fluid percussive injury,31,32 controlled cortical impact injury,33,34 closed-head weight drop injury,35 and acceleration-impact injury36 have shown increased neural stem cells activation. All of these experimental studies have shown the most prevalent and notable endogenous cell response after traumatic brain injury is an elevated cell proliferation within neurogenic areas of the dentate gyrus and subventricular zone. It is well accepted that enhanced production of new neurons following the traumatic brain injury was detected predominantly in the hippocampus in the more seriously injured animals in many experimental studies.37 More studies have discovered that injury-enhanced new granule neurons send out axonal projections into the targeted CA3 region implying their integration into the existing hippocampal circuitry,37,38 and this injury-induced endogenous neurogenic stem cells response is directly associated with the inherent cognitive functional recovery after traumatic brain injury of rodents.39,40

In the human brain, the extent and physiology of the adult neural generation are not well understood. A study on human brain samples taken from the autopsy revealed neural stem cells with proliferative ability have been observed within the subventricular zone and the hippocampus.41,42 Conversely, a more recent study has shown that neurogenesis in the subventricular zone and movement of new neurons from the subventricular zone to the olfactory bulbs and neocortex are restricted and only seen in the early childhood period.43,44 Therefore, credible evidence of traumatic brain injury-initiated neurogenesis in the human brain is inadequate because of the difficulties of collecting human brain samples and technical challenges to birth-dating neural stem cells.

After traumatic brain injury, injury-initiated neural cell loss is permanent. Given the restricted amount of endogenous neurogenic stem cells, neural transplantation supplementing exogenous stem cells to the damaged brain tissue is a potential treatment for post-traumatic brain injury regeneration.45 Especially, the transplanted cells will not only be able to replace the damaged neural cells but also give neurotrophic support in hopes of reestablishing and stabilizing the damaged brain tissue.45 Clinical evidence revealed intervention with stem cell secretome may significantly improve neural inflammation after traumatic brain injury and other neurological deficits in humans.46 Besides, the combined effects of bioscaffold and exosomes can aid in the transportation of stem cells to damaged areas as well as enhance their survival and facilitate successful treatment.47 Despite the rapid progression of brain infarction, the decreased proliferation of neural stem cells, and the delayed initiation of neurological recovery were observed in the aged rat model compared with a young rat after stroke, the restorative capability of the brain by stem cell therapy is still present in the aged rat.48 Compared to stem cell monotherapies which are still uniformly failed in clinical practice, combination therapy with hypothermia has potential therapeutic effects on the physiology of the aged brain and may be required for effective protection of the brain following stroke.49 After several years of biomaterials study for regeneration of peripheral nerve, a new 3D printing strategy is developing as a good substitution for nerve autograft over large gap injuries. The applications of 3D printing technologies can help in improving long-distance peripheral nerve regeneration since it is a leading device to give one path for better nerve guidance.50 Up to now, various categories of stem cell therapy have been tested for post-traumatic brain injury. These include embryonic stem cells, adult-derived neural stem cells, mesenchymal stem cells, and induced pluripotent stem cells.

Embryonic stem cells obtained from fetal or embryonic brain tissues are highly considered for neural transplantation because of their ability of plasticity and have the capacity to self-repair and differentiation into all germinal layers. They can differentiate, migrate, and innervate as transplanted into a receiver brain tissue.51 In previous clinical brain injury studies, neural stem cells derived from the embryonic human brain could survive for a long time, migrating to the contralateral cortex and differentiating into mature neural cells and microglia following transplantation into the damaged brain tissue.52 Implanted neurogenic stem cells obtained from human fetal stem cells may differentiate into adult neurons and release growth factors increasing the cognitive functional recovery of the damaged brain.53 Interestingly, the long-term survival rate of transplanted neural stem cells obtained from mice embryonic brains was seen for up to 1 year with a high degree of migration in the damaged brain and maturation into neurons or neuroglial cells along with enhanced motor and spatial learning functions of the brain tissue.5456 In addition, embryonic stem cells expressing growth factors or early differentiated into neurotransmitter expressing adult neurons after in vitro manipulation have revealed improved transplant survival and neuronal differentiation following grafted into the damaged brain, and the receivers have better recovery in motor and cognitive activities.5759 Even though embryonic stem cells have a high rate of survival and plasticity in neuronal transplantation, the ethical concerns, risk of transplant rejection, and the likelihood of teratoma development restrict their therapeutic use for traumatic brain injury.45

Neural stem cells are multipotent cells that can differentiate into neural cells but have a limited ability to differentiate into other tissue types.60 Neurogenic stem cells are located in the subventricular zones of the lateral ventricle, the hippocampal dentate gyrus, and other areas of the brain like the cerebral cortex, amygdala, hypothalamus, and substantia nigra. They could be isolated, developed in culture media, and produce many neural lineages that can be used in the treatment of neurological disorders as an important element of cellular-replacement therapy.61 Adult neural stem cells were transplanted into damaged parts of the brain in a traumatic brain injury rat model. These cells survived the transplantation process and moved to a damaged site when expressing markers for adult microglia and oligodendrocytes.62 Interestingly, one most recent study indicated that Korean red ginseng extract-mediated astrocytic heme oxygenase-1 induction contributes to the proliferation and differentiation of adult neural stem cells by upregulating astrocyteneuronal system cooperation.63 Another study revealed that following neural stem cell transplantation to the hippocampal region, injured rats had developed better cognitive function.64 The administration of combined therapies such as human neural stem/progenitor cells and curcumin-loaded noisome nanoparticles significantly improve brain edema, gliosis, and inflammatory responses in the traumatic brain injury rat model.65 Furthermore, in traumatic brain injury rat models, as neural stem cells were injected intravenously, they resulted in a decreased neurologic impairment and less edema because of the anti-inflammatory and anti-apoptotic features of neural stem cells.60,66 The ideal transplantation timeframe is 714 days,60 beyond which the glial scar forms, restricting perfusion and graft survival.67 The ability to transport cells to the desired location is a key obstacle with neural stem cell transplantation. Neural stem cells can be administered intrathecally, intravenously, and intra-arterial infusion. Conversely, a nanofiber scaffold implantation was proposed by Walker et al as a new strategy to be implemented to give the support essential for cell proliferation, which provides direction to future research.68

Mesenchymal stem cells are multipotent stromal that can differentiate into mesenchymal and non-mesenchymal tissue, such as neural tissue.69 They are obtained from different types of tissues.70 The accessibility, availability, and differentiation ability of these cells have drawn the attention of researchers performing studies in regenerative medicine. A previous study revealed the differentiation capacity of mesenchymal stem cells into neuronal cells. This study found that when rat and human mesenchymal stem cells are exposed to various experimental culture conditions, they can differentiate into neural and neuroglial cells.69 Besides, mesenchymal stem cells have also been demonstrated to enhance the proliferation and differentiation of native neural stem cells; the mechanism of which may be directly associated with chemokines produced by mesenchymal stem cells or indirectly through stimulation of adjacent astrocytes.70 In addition to their capacity to differentiate, mesenchymal stem cells selectively move to damaged tissues in traumatic brain injury rat models, where they develop into neurons and astrocytes and enhance motor function.71 The possible mechanism of action through which this occurs is linked to chemokines, growth factors,72 and adhesion factors, like the vascular cell adhesion molecule (VCAM-1), which permits mesenchymal stem cells to adhere to the endothelium of damaged organ.73 Mesenchymal stem cell transplantation has become a potential and safe treatment of choice for traumatic brain injuries because of its anti-inflammatory capability by regulating leukocyte and inflammatory factors such as IL-6, CRP, and TNF-a.74,75 Treatment with mesenchymal stem cell-derived extracellular vesicles greatly increased neurogenesis and neuroplasticity in a pig model of hemorrhagic stroke and traumatic brain damage.76 Currently, stem cell therapy using mesenchymal stromal cells has been widely investigated in preclinical models and clinical trials for the treatment of several neurological illnesses, including traumatic brain injury. Mesenchymal stem cells investigated for the treatment of traumatic brain injury in these clinical trials include bone marrow-derived stem cells, amnion-derived multipotent progenitor cells, adipose-derived stem cells, umbilical cord-derived stem cells, and peripheral blood-derived stem cells.7779 Those undifferentiated mesenchymal-derived cells have a heterogeneous cell population that includes stem and progenitor cells. They can be stimulated to differentiate into a neuronal cell phenotype in vitro. In the damaged brain tissue, these cells can generate a large number of growth factors, cytokines, and extracellular matrix substances that have neurotrophic or neuroprotective effects.80,81

From all mesenchymal stem cells, the effect of bone marrow-derived mesenchymal stem cells on traumatic brain injury has been fully investigated. According to previous studies, mesenchymal stem cells injected directly into the injured brain, or through intravenous or intra-arterial injections during the acute, sub-acute, or chronic phase following traumatic brain injury, have been shown to significantly reduce neurological abnormalities in motor and cognitive abilities.7779,82 The therapeutic effect of mesenchymal stem cells is mostly because of the bioactive molecules they produced to facilitate the endogenous plasticity and remodeling of the recipient brain tissue instead of direct neural repair as direct neuronal differentiation and long-term viability were rarely seen.80 A more recent study found that the injection of cell-free exosomes obtained from human bone marrow-derived mesenchymal stromal cells can increase the functional recovery of damaged animals after traumatic brain injury.83 Another study used a traumatic rodent model to evaluate the anti-inflammatory and immunoregulatory properties of mesenchymal stem cells. When compared to the control group, neurological function was improved in the treatment groups from 3 to 28 days. Mesenchymal stem cell therapy significantly decreased the amount of microglia or macrophages, neutrophils, CD3 lymphocytes, apoptotic cells in the damaged cortex, and proinflammatory cytokines.81 The main challenge of using mesenchymal stem cells for traumatic brain injury treatment is the long-term possibility of brain malignancy development because of the mesenchymal stromal cells ability to antitumor response suppression.84

In a recent study, seven traumatic brain injury patients were given a mesenchymal stem cells transplant during a cranial operation and then administered a second dose intravenously. At the end of the 6-month follow-up period, patients exhibited better neurological function with no signs of toxicity.85

Recent studies revealed that the administration of exosomes-derived human umbilical cord mesenchymal stem improves sensorimotor function and spatial learning activities in rat models following brain injuries. Furthermore, the applications of these cells extensively decreased proinflammatory cytokine expression via inhibiting the NF-B signaling pathway, reduced neuronal apoptosis, reduced inflammation, and increased neural regeneration ability in the injured cortex of rats following the injuries.86 Human umbilical cord-derived mesenchymal stem cells have better anti-inflammatory activity that may prevent and decrease secondary brain injury caused by the immediate discharge of inflammatory factors following traumatic brain injury.87 In traumatic brain injury rat models, the transplantation of umbilical cord-derived mesenchymal stem cells triggers the trans-differentiation of T-helper 17 into T regulatory, which in turn repairs neurological deficits and improves learning and memory function.88

To see the therapeutic effects of transplanted induced pluripotent stem cells compared to that of embryonic stem cells, Wang et al demonstrated animal models of ischemia and three different treatment options, which consist of pluripotent stem cells, embryonic stem cells, and phosphate-buffered saline for the control. The rodents were given an injection into the left lateral ventricle of the brain. Embryonic stem cell treatment group rodents showed a significant improvement in glucose metabolism within two-week period. However, 1 month following treatment, neuroimaging tests were done and it was revealed that both pluripotent stem cell and embryonic stem cell treatment groups had improved neurologic scores as compared to the control group, suggesting that the treatment groups showed better recovery of their cognitive function. Further investigation indicated that the implanted cells survived and traveled to the area of injury. Finally, the investigator of this study concluded that induced pluripotent stem cells may be a better option than embryonic stem cells.57 Different studies showed that induced pluripotent stem cells improved motor and cognitive function in the host mouse brain tissue, and these cells migrate the injured brain areas from the injection site.89,90 Until now, there are limited studies on induced pluripotent stem cell therapy for brain injuries. This is because of the difficulty of obtaining induced pluripotent stem cells, high therapy costs, and technique limitations.

In preclinical and clinical trials, advanced progress has been made in stem cell-based therapy for traumatic brain injury patients. Various studies reported the therapeutic effect of stem cells for regenerating damaged brain tissue. However, because of the complexity and variability of brain injuries, post-traumatic brain injury neuronal regeneration and repair remain a long-term goal. There are numerous unresolved challenges for successful stem cell treatment. For endogenous restoration via mature neural regeneration, methods guiding the movement of new neuronal cells to the area of damaged tissue and maintaining long-term survival are very important. In stem cell therapy, the inherent features of transplanted cells and the local host micro-environment influences the fate of grafted cells, an appropriate cell source, and a host environment, which are required for effective transplantation. Therefore, these problems should be solved in preclinical traumatic brain injury trials before stem cell-based treatments could be used in the clinic. The therapeutic application of neural stem cell treatment, whether via manipulation of endogenous or implantation of exogenous neural stem cells, is a method that has been shown in multiple studies to have substantial potential to increase brain function recovery in persons suffering from traumatic brain injury-related disability. However, further studies need to be done on the therapeutic application of stem cells for traumatic brain injury due to our poor understanding of possible consequences, unknown ethical issues, routes of administration, and the use of mixed treatment.

All authors declared no conflicts of interest for this study.

1. Taylor CA, Bell JM, Breiding MJ, Xu L. Traumatic brain injury-related emergency department visits, hospitalizations, and deathsUnited States, 2007 and 2013. MMWR Surveil Summaries. 2017;66(9):1.

2. Hyder AA, Wunderlich CA, Puvanachandra P, Gururaj G, Kobusingye OC. The impact of traumatic brain injuries: a global perspective. NeuroRehabilitation. 2007;22(5):341353. doi:10.3233/NRE-2007-22502

3. Maas AI, Stocchetti N, Bullock R. Moderate and severe traumatic brain injury in adults. Lancet Neurol. 2008;7(8):728741. doi:10.1016/S1474-4422(08)70164-9

4. Das M, Mayilsamy K, Mohapatra SS, Mohapatra S. Mesenchymal stem cell therapy for the treatment of traumatic brain injury: progress and prospects. Rev Neurosci. 2019;30(8):839855. doi:10.1515/revneuro-2019-0002

5. Jorge RE, Robinson RG, Moser D, Tateno A, Crespo-Facorro B, Arndt S. Major depression following traumatic brain injury. Arch Gen Psychiatry. 2004;61(1):4250. doi:10.1001/archpsyc.61.1.42

6. Bramlett HM, Dietrich WD. Pathophysiology of cerebral ischemia and brain trauma: similarities and differences. J Cerebral Blood Flow Metabol. 2004;24(2):133150. doi:10.1097/01.WCB.0000111614.19196.04

7. Xiong Y, Mahmood A, Lu D, et al. Histological and functional outcomes after traumatic brain injury in mice null for the erythropoietin receptor in the central nervous system. Brain Res. 2008;1230:247257. doi:10.1016/j.brainres.2008.06.127

8. Gage FH, Temple S. Neural stem cells: generating and regenerating the brain. Neuron. 2013;80(3):588601. doi:10.1016/j.neuron.2013.10.037

9. Lois C, Alvarez-Buylla A. Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia. Proc Natl Acad Sci U S A. 1993;90(5):20742077. doi:10.1073/pnas.90.5.2074

10. Moreno MM, Linster C, Escanilla O, Sacquet J, Didier A, Mandairon N. Olfactory perceptual learning requires adult neurogenesis. Proc Natl Acad Sci U S A. 2009;106(42):1798017985. doi:10.1073/pnas.0907063106

11. Sun D. Endogenous neurogenic cell response in the mature mammalian brain following traumatic injury. Exp Neurol. 2016;275(3):405410. doi:10.1016/j.expneurol.2015.04.017

12. Tajiri N, Kaneko Y, Shinozuka K, et al. Stem cell recruitment of newly formed host cells via a successful seduction? Filling the gap between neurogenic niche and injured brain site. PLoS One. 2013;8(9):e74857. doi:10.1371/journal.pone.0074857

13. Gage FH, Kempermann G, Palmer TD, Peterson DA, Ray J. Multipotent progenitor cells in the adult dentate gyrus. J Neurobiol. 1998;36(2):249266. doi:10.1002/(SICI)1097-4695(199808)36:2<249::AID-NEU11>3.0.CO;2-9

14. Ortega F, Gascn S, Masserdotti G, et al. Oligodendrogliogenic and neurogenic adult subependymal zone neural stem cells constitute distinct lineages and exhibit differential responsiveness to Wnt signaling. Nat Cell Biol. 2013;15(6):602613. doi:10.1038/ncb2736

15. Gritti A, Bonfanti L, Doetsch F, et al. Multipotent neural stem cells reside in the rostral extension and olfactory bulb of adult rodents. J Neurosci. 2002;22(2):437445. doi:10.1523/JNEUROSCI.22-02-00437.2002

16. Parent JM, Vexler ZS, Gong C, Derugin N, Ferriero DM. Rat forebrain neurogenesis and striatal neuron replacement after focal stroke. Ann Neurol. 2002;52(6):802813. doi:10.1002/ana.10393

17. Kempermann G, Gage FH. Neurogenesis in the adult hippocampus. Novartis Found Symp. 2000;231:220226.

18. Cameron HA, McKay RD. Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus. J Comp Neurol. 2001;435(4):406417. doi:10.1002/cne.1040

19. Imayoshi I, Sakamoto M, Ohtsuka T, et al. Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain. Nat Neurosci. 2008;11(10):11531161. doi:10.1038/nn.2185

20. Van Praag H, Christie BR, Sejnowski TJ, Gage FH. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci. 1999;96(23):1342713431. doi:10.1073/pnas.96.23.13427

21. Sun D, Bullock MR, McGinn MJ, et al. Basic fibroblast growth factor-enhanced neurogenesis contributes to cognitive recovery in rats following traumatic brain injury. Exp Neurol. 2009;216(1):5665. doi:10.1016/j.expneurol.2008.11.011

22. Brown J, CooperKuhn CM, Kempermann G, et al. Enriched environment and physical activity stimulate hippocampal but not olfactory bulb neurogenesis. Eur J Neurosci. 2003;17(10):20422046. doi:10.1046/j.1460-9568.2003.02647.x

23. Van Praag H, Schinder AF, Christie BR, Toni N, Palmer TD, Gage FH. Functional neurogenesis in the adult hippocampus. Nature. 2002;415(6875):10301034. doi:10.1038/4151030a

24. Kempermann G, Brandon EP, Gage FH. Environmental stimulation of 129/SvJ mice causes increased cell proliferation and neurogenesis in the adult dentate gyrus. Curr Biol. 1998;8(16):939944. doi:10.1016/S0960-9822(07)00377-6

25. Kempermann G, Kuhn HG, Gage FH. Genetic influence on neurogenesis in the dentate gyrus of adult mice. Proc Natl Acad Sci. 1997;94(19):1040910414. doi:10.1073/pnas.94.19.10409

26. Cameron H, Gould E. Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus. Neuroscience. 1994;61(2):203209. doi:10.1016/0306-4522(94)90224-0

27. Banasr M, Hery M, Brezun JM, Daszuta A. Serotonin mediates estrogen stimulation of cell proliferation in the adult dentate gyrus. Eur J Neurosci. 2001;14(9):14171424. doi:10.1046/j.0953-816x.2001.01763.x

28. Kempermann G, van Praag H, Gage FH. Activity-dependent regulation of neuronal plasticity and self-repair. Prog Brain Res. 2000;127:3548.

29. Gould E, Tanapat P, Cameron HA. Adrenal steroids suppress granule cell death in the developing dentate gyrus through an NMDA receptor-dependent mechanism. Dev Brain Res. 1997;103(1):9193. doi:10.1016/S0165-3806(97)00079-5

30. Gould E, Tanapat P. Stress and hippocampal neurogenesis. Biol Psychiatry. 1999;46(11):14721479. doi:10.1016/S0006-3223(99)00247-4

31. Chirumamilla S, Sun D, Bullock M, Colello R. Traumatic brain injury-induced cell proliferation in the adult mammalian central nervous system. J Neurotrauma. 2002;19(6):693703. doi:10.1089/08977150260139084

32. Rice A, Khaldi A, Harvey H, et al. Proliferation and neuronal differentiation of mitotically active cells following traumatic brain injury. Exp Neurol. 2003;183(2):406417. doi:10.1016/S0014-4886(03)00241-3

33. Dash P, Mach S, Moore A. Enhanced neurogenesis in the rodent hippocampus following traumatic brain injury. J Neurosci Res. 2001;63(4):313319. doi:10.1002/1097-4547(20010215)63:4<313::AID-JNR1025>3.0.CO;2-4

34. Gao X, Enikolopov G, Chen J. Moderate traumatic brain injury promotes proliferation of quiescent neural progenitors in the adult hippocampus. Exp Neurol. 2009;219(2):516523. doi:10.1016/j.expneurol.2009.07.007

35. Vickers NJ. Animal communication: when Im calling you, will you answer too? Curr Biol. 2017;27(14):R713R5. doi:10.1016/j.cub.2017.05.064

36. Bye N, Carron S, Han X, et al. Neurogenesis and glial proliferation are stimulated following diffuse traumatic brain injury in adult rats. J Neurosci Res. 2011;89(7):9861000. doi:10.1002/jnr.22635

37. Sun D, McGinn MJ, Zhou Z, Harvey HB, Bullock MR, Colello RJ. Anatomical integration of newly generated dentate granule neurons following traumatic brain injury in adult rats and its association to cognitive recovery. Exp Neurol. 2007;204(1):264272. doi:10.1016/j.expneurol.2006.11.005

38. Emery DL, Fulp CT, Saatman KE, Schtz C, Neugebauer E, McIntosh TK. Newly born granule cells in the dentate gyrus rapidly extend axons into the hippocampal CA3 region following experimental brain injury. J Neurotrauma. 2005;22(9):978988. doi:10.1089/neu.2005.22.978

39. Seth AK, Barrett AB, Barnett L. Granger causality analysis in neuroscience and neuroimaging. J Neurosci. 2015;35(8):32933297. doi:10.1523/JNEUROSCI.4399-14.2015

40. Sun D, Daniels TE, Rolfe A, Waters M, Hamm R. Inhibition of injury-induced cell proliferation in the dentate gyrus of the hippocampus impairs spontaneous cognitive recovery after traumatic brain injury. J Neurotrauma. 2015;32(7):495505. doi:10.1089/neu.2014.3545

41. Eriksson PS, Perfilieva E, Bjrk-Eriksson T, et al. Neurogenesis in the adult human hippocampus. Nat Med. 1998;4(11):13131317. doi:10.1038/3305

42. Sanai N, Tramontin AD, Quinones-Hinojosa A, et al. Unique astrocyte ribbon in the adult human brain contains neural stem cells but lacks chain migration. Nature. 2004;427(6976):740744. doi:10.1038/nature02301

43. Bergmann O, Liebl J, Bernard S, et al. The age of olfactory bulb neurons in humans. Neuron. 2012;74(4):634639. doi:10.1016/j.neuron.2012.03.030

44. Sanai N, Nguyen T, Ihrie RA, et al. Corridors of migrating neurons in the human brain and their decline during infancy. Nature. 2011;478(7369):382386. doi:10.1038/nature10487

45. Weston NM, Sun D. The potential of stem cells in the treatment of traumatic brain injury. Curr Neurol Neurosci Rep. 2018;18(1):110. doi:10.1007/s11910-018-0812-z

46. Muhammad SA, Abbas AY, Imam MU, Saidu Y, Bilbis LS. Efficacy of stem cell secretome in the treatment of traumatic brain injury: a systematic review and meta-analysis of preclinical studies. Mol Neurobiol. 2022;59:116. doi:10.1007/s12035-021-02552-1

47. Yuan J, Botchway BO, Zhang Y, Wang X, Liu X. Combined bioscaffold with stem cells and exosomes can improve traumatic brain injury. Stem Cell Rev Rep. 2020;16(2):323334. doi:10.1007/s12015-019-09927-x

48. Popa-Wagner A, Buga A-M, Doeppner TR, Hermann DM. Stem cell therapies in preclinical models of stroke associated with aging. Front Cell Neurosci. 2014;8:347. doi:10.3389/fncel.2014.00347

49. Joseph C, Buga A-M, Vintilescu R, et al. Prolonged gaseous hypothermia prevents the upregulation of phagocytosis-specific protein annexin 1 and causes low-amplitude EEG activity in the aged rat brain after cerebral ischemia. J Cerebral Blood Flow Metabol. 2012;32(8):16321642. doi:10.1038/jcbfm.2012.65

50. Petcu EB, Midha R, McColl E, Popa-Wagner A, Chirila TV, Dalton PD. 3D printing strategies for peripheral nerve regeneration. Biofabrication. 2018;10(3):032001. doi:10.1088/1758-5090/aaaf50

51. Hentze H, Graichen R, Colman A. Cell therapy and the safety of embryonic stem cell-derived grafts. Trends Biotechnol. 2007;25(1):2432. doi:10.1016/j.tibtech.2006.10.010

52. Wennersten A, Meijer X, Holmin S, Wahlberg L, Mathiesen T. Proliferation, migration, and differentiation of human neural stem/progenitor cells after transplantation into a rat model of traumatic brain injury. J Neurosurg. 2004;100(1):8896. doi:10.3171/jns.2004.100.1.0088

53. Gao J, Prough DS, McAdoo DJ, et al. Corrigendum to Transplantation of primed human fetal neural stem cells improves cognitive function in rats after traumatic brain injury [Exp. Neurol. 201 (2006) 281292]. Exp Neurol. 2007;204(1):490. doi:10.1016/j.expneurol.2006.10.001

54. Shear DA, Tate MC, Archer DR, et al. Neural progenitor cell transplants promote long-term functional recovery after traumatic brain injury. Brain Res. 2004;1026(1):1122. doi:10.1016/j.brainres.2004.07.087

55. Riess P, Zhang C, Saatman KE, et al. Transplanted neural stem cells survive, differentiate, and improve neurological motor function after experimental traumatic brain injury. Neurosurgery. 2002;51(4):10431054. doi:10.1097/00006123-200210000-00035

56. Boockvar JA, Schouten J, Royo N, et al. Experimental traumatic brain injury modulates the survival, migration, and terminal phenotype of transplanted epidermal growth factor receptor-activated neural stem cells. Neurosurgery. 2005;56(1):163171. doi:10.1227/01.NEU.0000145866.25433.FF

57. Becerra GD, Tatko LM, Pak ES, Murashov AK, Hoane MR. Transplantation of GABAergic neurons but not astrocytes induces recovery of sensorimotor function in the traumatically injured brain. Behav Brain Res. 2007;179(1):118125. doi:10.1016/j.bbr.2007.01.024

58. Ma H, Yu B, Kong L, Zhang Y, Shi Y. Neural stem cells over-expressing Brain-Derived Neurotrophic Factor (BDNF) stimulate synaptic protein expression and promote functional recovery following transplantation in rat model of traumatic brain injury. Neurochem Res. 2012;37(1):6983. doi:10.1007/s11064-011-0584-1

59. Blaya MO, Tsoulfas P, Bramlett HM, Dietrich WD. Neural progenitor cell transplantation promotes neuroprotection, enhances hippocampal neurogenesis, and improves cognitive outcomes after traumatic brain injury. Exp Neurol. 2015;264:6781. doi:10.1016/j.expneurol.2014.11.014

60. Reis C, Gospodarev V, Reis H, et al. Traumatic brain injury and stem cell: pathophysiology and update on recent treatment modalities. Stem Cells Int. 2017;2017:113. doi:10.1155/2017/6392592

61. Faigle R, Song H. Signaling mechanisms regulating adult neural stem cells and neurogenesis. Biochimica et Biophysica Acta. 2013;1830(2):24352448. doi:10.1016/j.bbagen.2012.09.002

62. Sun D, Gugliotta M, Rolfe A, et al. Sustained survival and maturation of adult neural stem/progenitor cells after transplantation into the injured brain. J Neurotrauma. 2011;28(6):961972. doi:10.1089/neu.2010.1697

63. Kim M, Moon S, Jeon HS, et al. Dual effects of Korean red ginseng on astrocytes and neural stem cells in traumatic brain injury: the HO-1Tom20 axis as a putative target for mitochondrial function. Cells. 2022;11(5):892. doi:10.3390/cells11050892

64. Park D, Joo SS, Kim TK, et al. Human Neural Stem Cells Overexpressing Choline Acetyltransferase Restore the Cognitive Function of Kainic Acid-Induced Learning and Memory Deficit Animals. Los Angeles, CA: SAGE Publications Sage CA; 2012.

65. Narouiepour A, Ebrahimzadeh-Bideskan A, Rajabzadeh G, Gorji A, Negah SS. Neural stem cell therapy in conjunction with curcumin loaded in niosomal nanoparticles enhanced recovery from traumatic brain injury. Sci Rep. 2022;12(1):113. doi:10.1038/s41598-022-07367-1

66. Lee S-T, Chu K, Jung K-H, et al. Anti-inflammatory mechanism of intravascular neural stem cell transplantation in hemorrhagic stroke. Brain. 2008;131(3):616629. doi:10.1093/brain/awm306

67. Bhalala OG, Pan L, Sahni V, et al. microRNA-21 regulates astrocytic response following spinal cord injury. J Neurosci. 2012;32(50):1793517947. doi:10.1523/JNEUROSCI.3860-12.2012

68. Walker PA, Aroom KR, Jimenez F, et al. Advances in progenitor cell therapy using scaffolding constructs for central nervous system injury. Stem Cell Rev Rep. 2009;5(3):283300. doi:10.1007/s12015-009-9081-1

69. Sanchez-Ramos J, Song S, Cardozo-Pelaez F, et al. Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol. 2000;164(2):247256. doi:10.1006/exnr.2000.7389

70. Meirelles LS, Chagastelles PC, Nardi NB. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci. 2006;119(11):22042213. doi:10.1242/jcs.02932

71. Wang S, Kan Q, Sun Y, et al. Caveolin-1 regulates neural differentiation of rat bone mesenchymal stem cells into neurons by modulating Notch signaling. Int J Dev Neuroscie. 2013;31(1):3035. doi:10.1016/j.ijdevneu.2012.09.004

72. Ponte AL, Marais E, Gallay N, et al. The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factor chemotactic activities. Stem Cells. 2007;25(7):17371745. doi:10.1634/stemcells.2007-0054

73. da Silva Meirelles L, Fontes AM, Covas DT, Caplan AI. Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine Growth Factor Rev. 2009;20(56):419427. doi:10.1016/j.cytogfr.2009.10.002

74. Viet QHN, Nguyen VQ, Le Hoang DM, Thi THP, Tran HP, Thi CHC. Ability to regulate immunity of mesenchymal stem cells in the treatment of traumatic brain injury. Neurol Sci. 2022;43(3):21572164. doi:10.1007/s10072-021-05529-z

75. Zhang Y, Dong N, Hong H, Qi J, Zhang S, Wang J. Mesenchymal stem cells: therapeutic mechanisms for stroke. Int J Mol Sci. 2022;23(5):2550. doi:10.3390/ijms23052550

76. Bambakidis T, Dekker SE, Williams AM, et al. Early treatment with a single dose of mesenchymal stem cell-derived extracellular vesicles modulates the brain transcriptome to create neuroprotective changes in a porcine model of traumatic brain injury and hemorrhagic shock. Shock. 2022;57(2):281290. doi:10.1097/SHK.0000000000001889

77. Lu D, Mahmood A, Wang L, Li Y, Lu M, Chopp M. Adult bone marrow stromal cells administered intravenously to rats after traumatic brain injury migrate into brain and improve neurological outcome. NeuroReport. 2001;12(3):559563. doi:10.1097/00001756-200103050-00025

78. Mahmood A, Lu D, Li Y, Chen JL, Chopp M. Intracranial bone marrow transplantation after traumatic brain injury improving functional outcome in adult rats. J Neurosurg. 2001;94(4):589595. doi:10.3171/jns.2001.94.4.0589

79. Bonilla C, Zurita M, Otero L, Aguayo C, Vaquero J, Vaquero J. Delayed intralesional transplantation of bone marrow stromal cells increases endogenous neurogenesis and promotes functional recovery after severe traumatic brain injury. Brain Injury. 2009;23(9):760769. doi:10.1080/02699050903133970

80. Li Y, Chopp M. Marrow stromal cell transplantation in stroke and traumatic brain injury. Neurosci Lett. 2009;456(3):120123. doi:10.1016/j.neulet.2008.03.096

81. Zhang R, Liu Y, Yan K, et al. Anti-inflammatory and immunomodulatory mechanisms of mesenchymal stem cell transplantation in experimental traumatic brain injury. J Neuroinflammation. 2013;10(1):112. doi:10.1186/1742-2094-10-106

82. Mahmood A, Lu D, Lu M, Chopp M. Treatment of traumatic brain injury in adult rats with intravenous administration of human bone marrow stromal cells. Neurosurgery. 2003;53(3):697703. doi:10.1227/01.NEU.0000079333.61863.AA

83. Zhang Y, Chopp M, Zhang ZG, et al. Systemic administration of cell-free exosomes generated by human bone marrow derived mesenchymal stem cells cultured under 2D and 3D conditions improves functional recovery in rats after traumatic brain injury. Neurochem Int. 2017;111:6981. doi:10.1016/j.neuint.2016.08.003

Read more:
Repair of Traumatic Brain Injury | SCCAA - Dove Medical Press

Bone Marrow Stem Cells Comments Off on Repair of Traumatic Brain Injury | SCCAA – Dove Medical Press | July 16th, 2022

Fibrosis is the thickening of various tissues caused by the deposition of fibrillar extracellular matrix (ECM) in tissues and organs as part of the bodys wound healing response to various forms of damage. When accompanied by chronic inflammation, fibrosis can go into overdrive and produce excess scar tissue that can no longer be degraded. This process causes many diseases in multiple organs, including lung fibrosis induced by smoking or asbestos, liver fibrosis induced by alcohol abuse, and heart fibrosis often following heart attacks. Fibrosis can also occur in the bone marrow, the spongy tissue inside some bones that houses blood-producing hematopoietic stem cells (HSCs) and can lead to scarring and the disruption of normal functions.

Chronic blood cancers known as myeloproliferative neoplasms (MPNs) are one example, in which patients can develop fibrotic bone marrow, or myelofibrosis, that disrupts the normal production of blood cells. Monocytes, a type of white blood cell belonging to the group of myeloid cells, are overproduced from HSCs in neoplasms and contribute to the inflammation in the bone marrow environment, or niche. However, how the fibrotic bone marrow niche itself impacts the function of monocytes and inflammation in the bone marrow was unknown.

Now, a collaborative team from Penn, Harvard, the Dana-Farber Cancer Institute (DFCI), and Brigham and Womens Hospital has created a programmable hydrogel-based in vitro model mimicking healthy and fibrotic human bone marrow. Combining this system with mouse in vivo models of myelofibrosis, the researchers demonstrated that monocytes decide whether to enter a pro-inflammatory state and go on to differentiate into inflammatory dendritic cells based on specific mechanical properties of the bone marrow niche with its densely packed ECM molecules. Importantly, the team found a drug that could tone down these pathological mechanical effects on monocytes, reducing their numbers as well as the numbers of inflammatory myeloid cells in mice with myelofibrosis. The findings are published in Nature Materials.

We found that stiff and more elastic slow-relaxing artificial ECMs induced immature monocytes to differentiate into monocytes with a pro-inflammatory program strongly resembling that of monocytes in myelofibrosis patients, and the monocytes to differentiate further into inflammatory dendritic cells, says co-first author Kyle Vining, who recently joined Penn.More viscous fast-relaxing artificial ECMs suppressed this myelofibrosis-like effect on monocytes. This opened up the possibility of a mechanical checkpoint that could be disrupted in myelofibrotic bone marrow and also may be at play in other fibrotic diseases. Vining will be appointedassistant professor of preventive and restorative sciences in theSchool of Dental Medicine and the Department of Materials Sciences in theSchool of Engineering and Applied Science, pending approval by Penn Dental Medicines personnel committees and the Provosts office.

Vining worked on the study as a postdoctoral fellow at Harvard in the lab of David Mooney. Our study shows that the differentiation state of monocytes, which are key players in the immune system, is highly regulated by mechanical changes in the ECM they encounter, says Mooney, who co-led the study with DFCI researcher Kai Wucherpfennig. Specifically, the ECMs viscoelasticity has been a historically under-appreciated aspect of its mechanical properties that we find correlates strongly between our in vitro and the in vivo models and human disease. It turns out that myelofibrosis is a mechano-related disease that could be treated by interfering with the mechanical signaling in bone marrow cells.

Mooney is also the Robert P. Pinkas Family Professor of Bioengineering at Harvard and leads the Wyss Institutes Immuno-Materials Platform. Wucherpfennig is director of DFCIs Center for Cancer Immunotherapy Research, professor of neurobiology at Brigham and Harvard Medical School, and an associate member of the Broad Institute of MIT and Harvard. Mooney, together with co-senior author F. Stephen Hodi, also heads the Immuno-engineering to Improve Immunotherapy (i3) Center, which aims to create new biomaterials-based approaches to enhance immune responses against tumors. The new study follows the Centers road map. Hodi is director of the Melanoma Center and The Center for Immuno-Oncology at DFCI and professor of medicine at Harvard Medical School.

The mechanical properties of most biological materials are determined by their viscoelastic characteristics. Unlike purely elastic substances like a vibrating quartz, which store elastic energy when mechanically stressed and quickly recover to their original state once the stress is removed, slow-relaxing viscoelastic substances also have a viscous component. Like the viscosity of honey, this allows them to dissipate stress under mechanical strain by rapid stress relaxation. Viscous materials are thus fast-relaxing materials in contrast to slow-relaxing purely elastic materials.

The team developed an alginate-based hydrogel system that mimics the viscoelasticity of natural ECM and allowed them to tune the elasticity independent from other physical and biochemical properties. By tweaking the balance between elastic and viscous properties in these artificial ECMs, they could recapitulate the viscoelasticity of healthy and scarred fibrotic bone marrow, whose elasticity is increased by excess ECM fibers. Human monocytes placed into these artificial ECMs constantly push and pull at them and in turn respond to the materials mechanical characteristics.

Next, the team investigated how the mechanical characteristics of stiff and elastic hydrogels compared to those in actual bone marrow affected by myelofibrosis. They took advantage of a mouse model in which an activating mutation in a gene known as Jak2 causes MPN, pro-inflammatory signaling in the bone marrow, and development of myelofibrosis, similar to the disease process in human patients with MPN. When they investigated the mechanical properties of bone marrow in the animals femur bones, using a nanoindentation probe, the researchers measured a higher stiffness than in non-fibrotic bone marrow. Importantly, we found that the pathologic grading of myelofibrosis in the animal model was significantly correlated with changes in viscoelasticity, said co-first author Anna Marneth, who spearheaded the experiments in the mouse model as a postdoctoral fellow working with Ann Mullally, a principal investigator at Brigham and DFCI, and another senior author on the study.

An important question was whether monocytes response to the mechanical impact of the fibrotic bone marrow niche could be therapeutically targeted. The researchers focused on an isoform of the phosphoinositide 3-kinase (PI3K)-gamma protein, which is specifically expressed in monocytes and closely related immune cells. PI3K-gamma is known for regulating the assembly of a cell-stiffening filamentous cytoskeleton below the cell surface that expands in response to mechanical stress, which the team also observed in monocytes encountering a fibrotic ECM. When they added a drug that inhibits PI3K-gamma to stiff elastic artificial ECMs, it toned down their pro-inflammatory response and, when given as an oral treatment to myelofibrosis mice, significantly lowered the number of monocytes and dendritic cells in their bone marrow.

This research opens new avenues for modifying immune cell function in fibrotic diseases that are currently difficult to treat. The results are also highly relevant to human cancers with a highly fibrotic microenvironment, such as pancreatic cancer, says Wucherpfennig.

Adapted from a press release written by Benjamin Boettner of the Wyss Institute for Biologically Inspired Engineering at Harvard University.

Other authors on the study are Harvards Kwasi Adu-Berchie, Joshua M. Grolman, Christina M. Tringides, Yutong Liu, Waihay J. Wong, Olga Pozdnyakova, Mariano Severgnini, Alexander Stafford, and Georg N. Duda.

The study was funded by the National Cancer Institute of the National Institutes of Health (Grant CA214369), National Institute of Dental & Craniofacial Research of the National Institutes of Health (grants DE025292 and DE030084), Food and Drug Administration (Grant FD006589), and Harvard University Materials Research Science and Engineering Center (Grant DMR 1420570).

Link:
Deconstructing the mechanics of bone marrow disease | Penn Today - Penn Today

Bone Marrow Stem Cells Comments Off on Deconstructing the mechanics of bone marrow disease | Penn Today – Penn Today | July 16th, 2022

Krabbe disease is one of many hundreds of inherited metabolic disorders. Named after the Danish neurologist Knud Krabbe, the disease causes progressive damage to the nervous system, eventually resulting in the death of the individual. The disease is common in newborns before they reach six months of age and treatment must start at the earliest. Most newborns affected by Krabbe disease do not reach the age of two.

Krabbe disease is caused due to genetic mutation on the 14th chromosome in an infant. A child needs to inherit two copies of the abnormal genome from both its parents, after which it has a 25 percent chance of inheriting both the recessive genes and developing the disease.

On inheriting the defective genome, the body doesnt produce enough of the enzyme galactosylceramidase (GALC). Galactosylceramidase is essential for breaking down unmetabolised lipids like glycosphingolipid and psychosine in the brain. These unmetabolised lipids are toxic to some of the non-neuron cells present in the brain.

Late-onset Krabbe disease, however, can be caused by a different genetic mutation which leads to a lack of a different enzyme, known as active saposin A.

Symptoms between early-onset and late-onset Krabbe disease differ slightly. Infants suffering from early-onset Krabbe disease suffer from symptoms like excessive irritability, difficulty swallowing, vomiting, unexplained fevers, and partial unconsciousness. Other common neuropathic symptoms include hypersensitivity to sound, muscle weakness, slowing of mental and motor development, spasticity, deafness, optic atrophy, optic nerve enlargement, blindness, and paralysis.

Late-onset Krabbe disease emerges with symptoms like the development of cross-eyes, slurred speech, slow development, and loss of motor functions.

The disease is diagnosed after a physician conducts a primary physical exam. A blood or skin tissue biopsy can test for GALC levels in the body and low levels can indicate the presence of Krabbe disease. Further testing through imaging scans (MRI), nerve conduction studies, eye examination, genetic testing and amniocentesis can also help diagnose the disease.

There is no cure for Krabbe disease. Treatment is mostly palliative in nature with a focus towards dealing with symptoms and providing supportive care. Experimental trials using hematopoietic stem cell transplant (HSCT), bone marrow transplantation, stem cell therapy, and gene therapy have seen some results in the small number of patients that they have been used on.

(Edited by : Shoma Bhattacharjee)

First Published:Jul 15, 2022, 06:32 AM IST

Go here to read the rest:
Krabbe disease, which mostly affects newborns causes, symptoms, and treatment - CNBCTV18

Bone Marrow Stem Cells Comments Off on Krabbe disease, which mostly affects newborns causes, symptoms, and treatment – CNBCTV18 | July 16th, 2022

Under embargo until Thursday 14 July 2022 at 16:00 (London time), 14 July 2022 at 11:00 (US Eastern Time).

Newswise The discovery of 14 inherited genetic changes which significantly increase the risk of a person developing a symptomless blood disorder associated with the onset of some types of cancer and heart disease is published today in Nature Genetics. The finding, made in one of the largest studies of its kind through genetic data analysis on 421,738 people, could pave the way for potential new approaches for the prevention and early detection of cancers including leukaemia.

Led by scientists from the Universities of Bristol and Cambridge, the Wellcome Sanger Institute, the Health Research Institute of Asturias in Spain, and AstraZeneca, the study reveals that specific inherited genetic changes affect the likelihood of developing clonal haematopoiesis, a common condition characterised by the development of expanding clones of multiplying blood cells in the body, driven by mutations in their DNA.

Although symptomless, the disorder becomes ubiquitous with age and is a risk factor for developing blood cancer and other age-related diseases. Its onset is a result of genetic changes in our blood-making cells.

All human cells acquire genetic changes in their DNA throughout life, known as somatic mutations, with a specific subset of somatic mutations driving cells to multiply. This is particularly common in professional blood-making cells, known as blood stem cells, and results in the growth of populations of cells with identical mutations known as clones.

Using data from the UK Biobank, a large-scale biomedical database and research resource containing genetic and health information from half a million UK participants, the team were able to show how these genetic changes relate not only to blood cancers but also to tumours that develop elsewhere in the body such as lung, prostate and ovarian cancer.

The team found that clonal haematopoiesis accelerated the process of biological ageing itself and influenced the risk of developing atrial fibrillation, a condition marked by irregular heartbeats.

The findings also clearly established that smoking is one of the strongest modifiable risk factors for developing the disorder, emphasising the importance of reducing tobacco use to prevent the conditions onset and its harmful consequences.

Dr Siddhartha Kar, UKRI Future Leaders Fellow at the University of Bristol and one of the studys lead authors from Bristols MRC Integrative Epidemiology Unit(IEU), said: Our findings implicate genes and the mechanisms involved in the expansion of aberrant blood cell clones and can help guide treatment advances to avert or delay the health consequences of clonal haematopoiesis such as progression to cancer and the development of other diseases of ageing.

Professor George Vassiliou, Professor of Haematological Medicine at the University of Cambridge and one of the studys lead authors, added: Our study reveals that the cellular mechanisms driving clonal haematopoiesis can differ depending on the mutated gene responsible. This is a challenge as we have many leads to follow, but also an opportunity as we may be able to develop treatments specific to each of the main subtypes of this common phenomenon.

Dr Pedro M. Quiros, formerly researcher at the Wellcome Sanger Institute and the University of Cambridge, and now Group Leader at the Health Research Institute of Asturias (Spain) and another of the studys lead authors says: We were particularly pleased to see that some of the genetic pathways driving clonal haematopoiesis appear to be susceptible to pharmacological manipulation and represent prioritised targets for the development of new treatments.

The study was funded by UK Research and Innovation (UKRI), Cancer Research UK (CRUK), Wellcome, the Royal Society, the Carlos III Health Institute, the Leukaemia and Lymphoma Society, and the Rising Tide Foundation for Clinical Cancer Research.

Paper

Genome-wide analyses of 200,453 individuals yield new insights into the causes and consequences of clonal hematopoiesis by Kar SP, et al. in Nature Genetics.

Ends

Further information:

Clonal haematopoiesis is the development of mutations in genes involved in blood cell production. It is diagnosedwhen a test on a person's blood or bone marrow sample shows that blood cells are carrying one of the genetic mutations associated with the condition. Clonal haematopoiesis becomes increasingly common with age, affecting more than one in every ten individuals older than 60 years.

Notes to editors

Paper: an embargoed copy of the paper is available to download here.

Issued by the University of Bristol Media Team.

Continued here:
Scientists Discover Genes That Affect the Risk of Developing Pre-Leukemia - Newswise

Bone Marrow Stem Cells Comments Off on Scientists Discover Genes That Affect the Risk of Developing Pre-Leukemia – Newswise | July 16th, 2022

This bone marrow market report provides details of new recent developments, trade regulations, import export analysis, production analysis, value chain optimization, market share, impact of domestic and localised market players, analyses opportunities in terms of emerging revenue pockets, changes in market regulations, strategic market growth analysis, market size, category market growths, application niches and dominance, product approvals, product launches, geographic expansions, technological innovations in the market. To gain more info on the bone marrow market contact Data Bridge Market Research for anAnalyst Brief,our team will help you take an informed market decision to achieve market growth.

The bone marrow market is expected to gain market growth in the forecast period of 2021 to 2028. Data Bridge Market Research analyses that the market is growing with the CAGR of 5.22% in the forecast period of 2021 to 2028 and is estimated to reach 13,899.60 USD Million by 2028. The growing amount of bone marrow diseases will help in escalating the growth of the bone marrow market. Bone marrow transplant also referred to as hematopoietic stem cell. It is a soft vascular tissue present in the interior of long bones. It comprises of two types of stem cells, that are hematopoietic and mesenchymal stem cells. Bone marrow is mainly responsible for the haematopoiesis, (formation of blood cells), production of lymphocytes, and the storage of fats. The bone marrow transplant is the last alternative generally recommended by the physicians in the cases of fatal bone marrow diseases and bone or skin cancer.

Get a Sample PDF of the report https://www.databridgemarketresearch.com/request-a-sample/?dbmr=global-bone-marrow-market

Major factors that are boosting the growth of the bone marrow market in the forecast period are the growing of the incidences of non-Hodgkin and Hodgkin lymphoma, thalassemia, and leukemia, along with the common bone marrow diseases around the world, the developments in the technology and the enhancing of the healthcare infrastructure. Furthermore, the advancing signs of bone marrow transplant for heart and neuronal disorders, increasing funding in the logistic services and the growing per capita of the healthcare expenses are some of the other factors anticipated to further propel the growth of the bone marrow market in the coming years. However, the high expenditure for the treatment, shortage of the bone marrow donors and instability of the repayment are few of the factors further responsible for the impeding the growth of the bone marrow market in the near future.

Bone MarrowMarket Scope and Market Size

The bone marrow market is segmented on the basis of transplantation type, disease indication and end user. The growth amongst these segments will help you analyse meagre growth segments in the industries, and provide the users with valuable market overview and market insights to help them in making strategic decisions for identification of core market applications.

To Gain More Insights into the Market Analysis, Browse Summary of the Research Report@ https://www.databridgemarketresearch.com/reports/global-bone-marrow-market

Bone MarrowMarket Country Level Analysis

The bone marrow market is analysed and market size insights and trends are provided by country, transplantation type, disease indication and end user as referenced above. The countries covered in the bone marrow market report are the U.S., Canada and Mexico in North America, Germany, France, U.K., Netherlands, Switzerland, Belgium, Russia, Italy, Spain, Turkey, Rest of Europe in Europe, China, Japan, India, South Korea, Singapore, Malaysia, Australia, Thailand, Indonesia, Philippines, Rest of Asia-Pacific (APAC) in the Asia-Pacific (APAC), Saudi Arabia, U.A.E, South Africa, Egypt, Israel, Rest of Middle East and Africa (MEA) as a part of Middle East and Africa (MEA), Brazil, Argentina and Rest of South America as part of South America.

Europe dominates the bone marrow market because of the occurrence of the increasing number of innovative healthcare centers. Furthermore, the healthcare systems have introduced the bone marrow transplant in their contributions and the state-of-the-art public facilities which will further boost the growth of the bone marrow market in the region during the forecast period. North America is projected to observe significant amount of growth in the bone marrow market because of the growing cases of chronic diseases such as blood cancer. Moreover, the increasing of the geriatric population is one of the factors anticipated to propel the growth of the bone marrow market in the region in the coming years.

The country section of the bone marrow market report also provides individual market impacting factors and changes in regulation in the market domestically that impacts the current and future trends of the market. Data points such as consumption volumes, production sites and volumes, import export analysis, price trend analysis, cost of raw materials, down-stream and upstream value chain analysis are some of the major pointers used to forecast the market scenario for individual countries. Also, presence and availability of global brands and their challenges faced due to large or scarce competition from local and domestic brands, impact of domestic tariffs and trade routes are considered while providing forecast analysis of the country data.

Competitive Landscape and Bone MarrowMarket Share Analysis

The bone marrow market competitive landscape provides details by competitor. Details included are company overview, company financials, revenue generated, market potential, investment in research and development, new market initiatives, global presence, production sites and facilities, production capacities, company strengths and weaknesses, product launch, product width and breadth, application dominance. The above data points provided are only related to the companies focus related to bone marrow market.

The major players covered in the bone marrow market report are AGendia, Agilent Technologies, Inc., Ambrilia Biopharma Inc., Astellas Pharma Inc., diaDexus, Illumina, Inc., QIAGEN, F Hoffmann-La Roche Ltd, Sanofi, Stryker Corporation, PromoCell GmbH, STEMCELL Technologies Inc., Lonza, ReachBio LLC, AllCells, ATCC, Lifeline Cell Technology., Conversant bio, HemaCare, Mesoblast Ltd., Merck KGaA, Discovery Life Sciences., ReeLabs Pvt. Ltd., Gamida Cell, among other domestic and global players. Market share data is available for global, North America, Europe, Asia-Pacific (APAC), Middle East and Africa (MEA) and South America separately. DBMR analysts understand competitive strengths and provide competitive analysis for each competitor separately.

Browse the complete table of contents at https://www.databridgemarketresearch.com/toc/?dbmr=global-bone-marrow-market

Related Reports:

Allogenic Stem Cell Therapy Market Size, Shares, Trends and Industry Growth Outlook https://www.databridgemarketresearch.com/reports/global-allogenic-stem-cell-therapy-market

Cancer Stem Cell Therapy Market Size, Shares, Trends and Industry Growth Outlook https://www.databridgemarketresearch.com/reports/global-cancer-stem-cell-therapy-market

North America Stem Cell Therapy Market Size, Shares, Trends and Industry Growth Outlook https://www.databridgemarketresearch.com/reports/north-america-stem-cell-therapy-market

Europe Stem Cell Therapy Market Size, Shares, Trends and Industry Growth Outlook https://www.databridgemarketresearch.com/reports/europe-stem-cell-therapy-market

Asia-Pacific Stem Cell Therapy Market Size, Shares, Trends and Industry Growth Outlook https://www.databridgemarketresearch.com/reports/asia-pacific-stem-cell-therapy-market

Middle East and Africa Stem Cell Therapy Market Size, Shares, Trends and Industry Growth Outlook https://www.databridgemarketresearch.com/reports/middle-east-and-africa-stem-cell-therapy-market

Asia-Pacific Drug-Device Combination Market Size, Shares, Trends and Industry Growth Outlook https://www.databridgemarketresearch.com/reports/global-drug-device-combination-market

About Data Bridge Market Research:

An absolute way to forecast what future holds is to comprehend the trend today! Data Bridge Market Research set forth itself as an unconventional and neoteric Market research and consulting firm with unparalleled level of resilience and integrated approaches. We are determined to unearth the best market opportunities and foster efficient information for your business to thrive in the market. Data Bridge endeavours to provide appropriate solutions to the complex business challenges and initiates an effortless decision-making process. Data Bridge is an aftermath of sheer wisdom and experience which was formulated and framed in the year 2015 in Pune.

Data Bridge Market Research has over 500 analysts working in different industries. We have catered more than 40% of the fortune 500 companies globally and have a network of more than 5000+ clientele around the globe. Data Bridge adepts in creating satisfied clients who reckon upon our services and rely on our hard work with certitude. We are content with our glorious 99.9 % client satisfying rate.

Contact Us:-

Data Bridge Market Research

US: +1 888 387 2818

UK: +44 208 089 1725

Hong Kong: +852 8192 7475

Email:- corporatesales@databridgemarketresearch.com

Original post:
Bone Marrow Market Global Projection By Key Players AGendia, Agilent Technologies, Inc., Ambrilia Biopharma Inc Analysis and Forecast to 2028 ...

Bone Marrow Stem Cells Comments Off on Bone Marrow Market Global Projection By Key Players AGendia, Agilent Technologies, Inc., Ambrilia Biopharma Inc Analysis and Forecast to 2028 … | July 8th, 2022

Sickle cell disease (SCD) is a debilitating illness affecting up to 40% of the population in some African countries. Its caused by mutations in the gene that makes haemoglobin the protein that carries oxygen in red blood cells.

It might one day be possible to treat this disease using gene editing by switching back on the production of a healthy form of haemoglobin called foetal haemoglobin, which is usually only produced by the body when were in the womb.

But a new study testing this promising new treatment in mice has found that scientists still have a long way to go before it can be attempted in humans. The research has been published in Disease Models & Mechanisms.

Healthy red blood cells (RBCs) are shaped similar to a donut but with an indentation instead of a hole.

In sickle cell disease the abnormal haemoglobin distorts the RBCs shape when they arent carrying oxygen. Instead, sickled RBCs are C-shaped, like the farm tool called a sickle, and they become hard and sticky, and die earlier.

Because of their shape, sickled RBCs can become stuck and stop blood flow when travelling through small blood vessels. This causes patients to suffer from episodes of excruciating pain, organ damage and a reduced life-expectancy.

Although current treatments have reduced complications and extended the life expectancies of affected children, most still die prematurely.

Red blood cells are made from haematopoietic stem cells in our bone marrow. These stem cells are able to develop into more than one cell type, in a process called haematopoiesis.

Researchers hope to edit the genes of these stem cells so that they produce RBCs with foetal haemoglobin instead of the abnormal protein and can be reintroduced into the body to alleviate the symptoms of SCD.

Get an update of science stories delivered straight to your inbox.

Unfortunately, they found that although two types of lab mice had the symptoms of sickle cell disease, their foetal haemoglobin gene and surrounding DNA were not properly configured, making the stem-cell treatment ineffective or even harmful.

These mice called Berkley and Townes mice were genetically engineered in different ways to carry several human haemoglobin genes (replacing the mice genes) so scientists could study sickle cell disease in an animal model.

The researchers removed stem cells from the mice and used CRISPIR-Cas9 to try to turn on the healthy foetal haemoglobin gene. They then put the reprogrammed stem cells back into the mice and monitored the animals for 18 weeks to find out how the treatment affected them.

Surprisingly, 70% of Berkley mice died from the therapy and production of foetal haemoglobin was activated in only 3.1% of the stem cells. On the other hand, treatment did not affect the survival of Townes mice and even activated the foetal haemoglobin gene in 57% of RBCs.

Even then, the levels of foetal haemoglobin produced were seven to 10 times lower than seen when this approach was used in human cells grown in the laboratory and were not high enough to reduce clinical signs of sickle cell disease.

We realised that we did not know enough about the genetic configurations of these mice, says senior author Dr Mitchell Weiss, chair of the haematology department at St Jude Childrens Research Hospital, US.

The researchers sequenced the mices haemoglobin genes and surrounding DNA, and discovered that Berkley mice instead of having a single copy of the mutated human gene had 22 randomly arranged, broken-up copies of the mutated human sickle cell disease gene and 27 copies of the human foetal haemoglobin.

This caused the fatal effects seen and meant that the mice cannot be used to test this treatment in the future.

Our findings will help scientists using the Berkeley and Townes mice decide which to use to address their specific research question relating to sickle cell disease or haemoglobin, concludes Weiss.

Additionally, this work provides a reminder for scientists to carefully consider the genetics of the mice that they are using to study human diseases and find the right mouse for the job.

Read more:
Sickle cell disease gene therapy study set back by the mice - Cosmos

Bone Marrow Stem Cells Comments Off on Sickle cell disease gene therapy study set back by the mice – Cosmos | July 8th, 2022

Returning home after a Fathers Day trip to New York City with his daughter in 2016, Scott Kesel thought he had come down with the flu. Bloodwork showed his blood platelets were lower than normal. He followed up with his regular physician and was given the news: he had chronic myelomonocytic leukemia (CMML).

CMML is a rare type of blood cancer that starts in the bone marrow, where blood cells are made. It can involve other areas of the body. There are only about 1,100 cases in the U.S. each year and its more common in people over age 60.

As a Canandaigua resident, Scott started his cancer journey at Wilmot Cancer Institutes Sands Cancer Center at F.F. Thompson. His oncologist laid out all the options: chemo and a stem cell transplant.

Knowing he would need a transplant, his team at Sands had him transfer to Wilmots Hematology team, where he began seeing Jason Mendler, M.D., and his transplant doctor, Omar Aljitawi, M.B.B.S.

He had chemotherapy at Wilmot, where he got to know the infusion nursing staff.

They have put a mindset in place thats so beneficial to the patient, he says.

For a stem cell transplant, his brother was the closest match they could find, although he was only a half-match. That left the option for a haplo-identical transplant available. Historically, it was required to have a closer match in order to do a transplant. With a haploidentical transplant, the donor is only half-matched. Its a newer procedure that is not available at all transplant centers, but the doctors at Wilmot have been performing the surgery since 2015.

He underwent the transplant but, unfortunately, in Scotts case, it didnt work.

For a short period, Scott went to another institution for a clinical trial. Unfortunately, that didnt work either. He developed pancreatitis and had to drop out of the trial. He also experienced cold agglutinin disease, which caused his immune system to attack his red blood cells. Cold temperatures can trigger it and he had to stay at Wilmot for about a month in a temperature-controlled room, set at 80 degrees at all times, to overcome it.

Once that resolved, the team at Wilmot suggested another treatment option to try on Scotts leukemia: a transplant with stem cells from an umbilical cord donation. Umbilical cord blood stem cells came from Australia and Spain to try to save Scotts life. He had only two cord blood units available and he needed both to have a successful transplant, which was his only viable chance to potentially cure his leukemia. Along with the cord blood, he also had radiation therapy with Louis Constine, M.D.

He had nothing but good things to say about the team that took care of him while he was hospitalized on Wilmot Cancer Centers sixth floor, the Blood and Marrow Transplant Unit.

It was exceptional. They were so friendly and accommodating right from the very beginning, he says. It wasnt limited to nurses. Theres medical technicians on the floor that were so friendly and became very good friends.

Scott Kesel (right) with Jason Mendler, M.D., at the 2019 Wilmot Warrior Walk

Thankfully, this time the transplant took. As of June 2022, Scott has been in remission for three-and-a-half years. He credits his team for getting him there.

Its an incredible group of people, he says.

But its not just his team hes grateful for. He appreciates that his life has returned basically back to normal, despite the tumultuous COVID pandemic that happened shortly after his transplant.

Hes gotten back to work and to hobbies he enjoys outside work.

I happen to be the worlds greatest tuba playing car salesman, he jokes.

This summer and fall, he has 28 gigs lined up, with different music groups around the region to keep him busy, and he looks forward to hunting and fishing during his free time.

For it all, he feels fortunate.

You have to be grateful for the outcome, he says. I got a lot of support remotely from people in my community who used the opportunity to promote bone marrow registration and blood drives, which was awful nice.

He adds, Im grateful that I ended up at Wilmot. I really couldnt have been in a better place.

Link:
'World's Greatest Tuba-Playing Car Salesman' Bounces Back after Leukemia, Thanks to Wilmot Team - URMC

Bone Marrow Stem Cells Comments Off on ‘World’s Greatest Tuba-Playing Car Salesman’ Bounces Back after Leukemia, Thanks to Wilmot Team – URMC | July 8th, 2022

The Global Rheumatoid Arthritis Stem Cell Therapy Market is replete with new growth opportunities and expansion avenues. There has been an increase in the use of products and services falling under the ambit of Rheumatoid Arthritis Stem Cell Therapy, giving a thrust to the growth of the global Rheumatoid Arthritis Stem Cell Therapy market. The unprecedented use of these products can be attributed to the increasing paying capacity of the masses.

Furthermore, in the absence of robust or utilitarian alternatives, the demand within the global Rheumatoid Arthritis Stem Cell Therapy market is projected to reach new heights of recognition. It is worthwhile to mention that the global Rheumatoid Arthritis Stem Cell Therapy market is treading along a lucrative pathway due to favorable government legislations.

To get in-depth insights Request for Brochure here https://www.factmr.com/connectus/sample?flag=B&rep_id=1001

The COVID-19 pandemic has changed narratives related to growth and expansion across several key industries. Therefore, the Rheumatoid Arthritis Stem Cell Therapy market is also battling the cons of supply chain disruptions and procurement issues. Over the course of the next quarter, market players could be investing in new technologies to recover from the shocks of the pandemic.

The global market for rheumatoid arthritis stem cell therapy is highly fragmented. Examples of some of the key players operating in the global rheumatoid arthritis stem cell therapy market include Mesoblast Ltd., Roslin Cells, Regeneus Ltd, ReNeuron Group plc, International Stem Cell Corporation, TiGenix and others.

Through the latest research report on Rheumatoid Arthritis Stem Cell Therapy market, the readers get insights on:

Share Your Requirements & Get Customized Reports: https://www.factmr.com/connectus/sample?flag=RC&rep_id=1001

Tentatively, the global rheumatoid arthritis stem cell therapy market can be segmented on the basis of treatment type, application, end-user, and geography.

Based on treatment type, the global rheumatoid arthritis stem cell therapy market can be segmented into:

Based on application, the global rheumatoid arthritis stem cell therapy market can be segmented into:

Based on the distribution channel, the global rheumatoid arthritis stem cell therapy market can be segmented into:

Based on geography, the global rheumatoid arthritis stem cell therapy market can be segmented into:

The study further identifies major manufacturing trends, technologies that will be commercialized

Reasons to choose a Fact.MR:

For In-depth Analysis & Business Strategy, Buy a Copy of this Report: https://www.factmr.com/checkout/1001

About Fact. MR

Market research and consulting agency with a difference! Thats why 80% of Fortune 1,000 companies trust us for making their most critical decisions. We have offices in US and Dublin, whereas our global headquarter is in Dubai. While our experienced consultants employ the latest technologies to extract hard-to-find insights, we believe our USP is the trust clients have in our expertise. Spanning a wide range from automotive & industry 4.0 to healthcare & retail, our coverage is expansive, but we ensure even the most niche categories are analyzed. Reach out to us with your goals, and well be an able research partner.

Contact:US Sales Office :11140 Rockville PikeSuite 400Rockville, MD 20852United StatesTel: +1 (628) 251-1583E-Mail:sales@factmr.com

Corporate Headquarter:Unit No: AU-01-H Gold Tower (AU),Plot No: JLT-PH1-I3A,Jumeirah Lakes Towers,Dubai, United Arab Emirates

View post:
Growing Prevalence & Recurrence Of Rheumatoid Arthritis Is Expected To Growth Of The Rheumatoid Arthritis Stem Cell Therapy Market Designer Women...

Bone Marrow Stem Cells Comments Off on Growing Prevalence & Recurrence Of Rheumatoid Arthritis Is Expected To Growth Of The Rheumatoid Arthritis Stem Cell Therapy Market Designer Women… | July 8th, 2022

Preclinical evaluation of FasT CAR-T cellsFasT CAR-T (F-CAR-T) proliferation in vitro

To characterize the in vitro proliferative capacity of F-CAR-T cells, F-CAR-T and C-CAR-T cells were manufactured in parallel (Supplementary Methods, and Fig. S1) using T-cells from 6 B-ALL patients. To investigate the ex vivo proliferation of F-CAR-T, frozen CD19 F-CAR-T and C-CAR-T cells from each patient were thawed and stimulated with irradiated CD19-expressing K562 cells. The number of CD19-targeting CAR-T cells was then determined during the course of cell expansion in vitro. As shown in Fig. 1A, upon CD19 antigen stimulation, F-CAR-T proliferation was much more robust compared to C-CAR-T proliferation. On day 17 post co-culture, F-CAR-T expanded 1205.61226.3 fold (MeanSD), while C-CAR-T expanded only 116.437.2 fold (MeanSD), (p=0.001). To characterize the mechanism underlying the superior proliferative ability of F-CAR-T, we purified CD19+ CAR-T cells from both F-CAR-T and C-CAR-T. The expression of genes involved in cell proliferation, cell cycle, and apoptosis was analyzed using Nanostring (detailed gene sets are in Table S2). Gene expression profiles showed higher F-CAR-T expression scores for genes associated with cell cycle regulation (F-CAR-T vs. C-CAR-T, p<0.01) and lower expression scores for apoptosis-related genes (F-CAR-T vs. C-CAR-T, p<0.05) in F-CAR-T cells (Fig. S2A).

A Ex vivo cell proliferation of F-CAR-T and C-CAR-T derived from B-ALL patients (n=6) (***P=0.001, F-CAR-T vs. C-CAR-T, d17, unpaired student two-tailed t-test). B Tscm, Tcm, and Tem were characterized by surface staining of CD45RO and CD62L and analyzed with flow cytometry (***P<0.001 comparing F-CAR-T and C-CAR-T). C T-cell exhaustion was characterized by PD-1, LAG3, and TIM-3 staining; Statistical analyses of the percentage of PD1+ LAG3+ Tim3+ (***P<0.001, comparing F-CAR-T and C-CAR-T), unpaired student two-tailed t-test). D RTCA assay was used to examine the specific killing of HeLa-CD19 cells. Growth of target HeLa-CD19 or HeLa cells were monitored dynamically. E CD19+ target Nalm6-Luc cells or F Raji-Luc cells were co-cultured with either F-CAR-T or C-CAR-T for 6h. Target cell killing efficacy was calculated by luciferase activity. NS, P>0.05 F-CAR-T vs. C-CAR-T (unpaired student t-test, two-tailed). F-CAR-T FasT CAR-T, C-CAR-T conventional CAR-T, Tcm (CD45RO+CD62L+) T central memory cells, Tem (CD45RO+CD62L) T effector memory cells, Tscm (CD45ROCD62L+) T stem cell memory, PD1 programmed cell death protein 1, TIM-3 T cell immunoglobulin and mucin domain containing-3, LAG3 lymphocyte-activation gene 3, RTCA real-time cell analyzer, E:T effector cells: target cells, NT normal T-cell.

Phenotypes of unstimulated F-CAR-T from three healthy donors were analyzed by flow cytometry. The CD45ROCD62L+ population was 45.7%2.2% which was comparable to the un-transduced T-cells (data not shown). Upon stimulation with CD19+ tumor cells for 9 days, C-CAR-T central memory cells (Tcm, CD45RO+CD62L+ and effector memory cells (Tem, CD45RO+CD62L) were 56.62%11.97% and 40.48%9.70%, respectively, among the C-CAR-T cells (Fig. 1B and Figs. S2B and S2). In contrast, Tcm cells (87.92%4.36%) was predominant in F-CAR-T, with only a small fraction of Tem (7.84%3.79%). In addition, F-CAR-T cells demonstrated more abundant T stem cell memory (Tscm) (3.841.22% vs 2.342.48%, p<0.05) than C-CAR-T cells. We also examined the exhaustion status of the stimulated CAR-T cells. A higher percentage of PD-1+LAG3+Tim3+T-cells were detected in the C-CAR-T (11.19%2.54%) compared to F-CAR-T (3.59%2.51%, p<0.001) (Fig. 1C). Together these data indicated that the F-CAR-T exhibited a younger phenotype and was less exhausted compared to C-CAR-T.

We used a real-time cell analyzer (RTCA) assay to measure the cytotoxicity of F-CAR-T and C-CAR-T against CD19+ cells in vitro. F-CAR-T and C-CAR-T killing of Hela-CD19 target cells were comparable using this assay (Fig. 1D). Similar levels of IFN- and IL-2 production were also observed (Fig. S2D). In a luciferase-based cytotoxicity assay, CD19+ B leukemia cell lines, Raji and Nalm6, were both effectively killed to similar or better levels at different E:T ratios (Fig. 1E, F).

To compare the in vivo cytotoxicity of F-CAR-T and C-CAR-T, severe immunodeficient NOG mice were engrafted with Raji-luciferase cells. One week after the tumor grafts were established, F-CAR-T and C-CAR-T were intravenously injected at various doses. The engrafted tumors progressed aggressively in control groups with either vehicle alone or control T-cells (Fig. 2A). In contrast, F-CAR-T or C-CAR-T treatment greatly suppressed tumor growth in a dose-dependent manner (Fig. 2A). In the high dose group (2106/mice), both F-CAR-T and C-CAR-T eliminated the tumor rapidly. However, in the low dose group (5105/mice), F-CAR-T showed more effective tumor-killing compared to C-CAR-T. On day 20, mice in the low dose F-CAR-T group became tumor-free, while C-CAR-T treated mice exhibited tumor relapse (Fig. 2A). We examined the CAR-T cell expansion in vivo after infusion. As shown in Fig. 2B, both F-CAR-T and C-CAR-T began to expand in the peripheral blood 7 days after infusion. C-CAR-T cell numbers reached their peak on day 14 and receded on day 21. In contrast, the F-CAR-T cell number peaked on day 21 and declined to a baseline level on day 28. F-CAR-T not only persisted longer but also underwent 26 folds greater expansion than C-CAR-T (Fig. 2B).

A Raji-Luc cell engraftment NOG mice were given high dose (2106/mice, n=3) and low dose (5105/mice, n=3) F-CAR-T/C-CAR-T along with control groups. Tumor growth was monitored with IVIS scan once every 3 days; B CAR-T expansion in peripheral blood of mice was analyzed by flow cytometry (n=6). ***P<0.001 for F-CAR-T HD vs. C-CAR-T HD; F-CAR-T LD vs. C-CAR-T LD; F-CAR-T HD vs. F-CAR-T LD; C-CAR-T HD vs. C-CAR-T LD (two-way ANOVA statistical analysis); C Schematic of the Nalm6 (1106) xenograft model, CAR-T (2106) infused 1 day after cyclophosphamide (20mg/kg) treatment. Bone marrow infiltration of F-CAR-T was analyzed 10 days after CAR-T infusion (n=3); D CD45+CD2 F-CAR-T vs. C-CAR-T in peripheral blood of mice were analyzed by flow cytometry; *P<0.05 (unpaired student two-tailed t-test). IVIS in vivo imaging system, PB peripheral blood, i.v. intravenous, HD high dose, LD low dose, Cy cyclophosphamide; *p<0.05; #: number.

We examined the BM infiltration of F-CAR-T cells after infusion into Nalm6-bearing mice (Fig. 2C). A larger population of CAR-T cells was observed 10 days after infusion in BM in F-CAR-T infused group than that in the C-CAR-T group (p<0.05) (Fig. 2D), suggesting F-CAR-T cells possessed a better BM homing capability than C-CAR-T.

The chemokine receptor CXCR4 is known to be critical for BM homing of T-cells [25, 26]. Indeed, a higher percentage of CXCR4+ T cells were detected in F-CAR-T than in the C-CAR-T. Interestingly, this phenotype was more pronounced for CD4+ T cells than CD8+ T cells (Fig. S3A). In a two-chamber system, more F-CAR-T cells could be detected in the lower chamber than their C-CAR-T counterparts (Fig. S3B).

Between Jan. 2019 and Oct. 2019, 25 pediatric and adult patients with CD19+R/R B-ALL were enrolled onto our phase 1 trial, including two patients who had relapsed following a prior allo-HSCT. Patient characteristics are detailed in Table 1. The median age of patients was 20 (range: 344) years old. Twenty patients were >14 years old, and five were 14 years old. The median percentage of pre-treatment BM blasts was 9.05% (range: 0.1982.9%). As our pre-clinical studies demonstrated that F-CAR-T cells had a superior expansion capability as compared to C-CAR-T, we infused a relatively low doses of F-CAR-T cells, ranging from 104105 cells/kg: 3.0104 cells/kg (n=2), 6.5 (5.867.43)104 cells/kg (n=9), 1.01 (1.01.16)105 cells/kg (n=12), 1.52(1.471.56)105 cells/kg (n=2), (Fig. S4). The median time from apheresis to the infusion of CD19+F-CAR-T cells was 14 days (range: 1220). Although the manufacturing time of F-CAR-T was next day, the quality control time and detailed final product releases including sterility testing require a minimum of 710 days to complete. In addition, transportation of cell products requires approximately two days. Of the 25 patients who received CD19 F-CAR-T infusion, 22 (88%) received bridging chemotherapy between apheresis and lymphodepleting chemotherapy to control rapid disease progression (Table S3).

F-CAR-T cells were manufactured successfully for all patients. The mean transduction efficiency of F-CAR-T was 35.4% (range: 13.170.3%) (Fig. S5A). Both CD4+/CAR+ (mean, 49.6%; range: 13.673.2%) and CD8+/CAR+ (mean, 41.5%; range: 20.677.7%) subsets were present in the CD3+CAR+ T cell subsets of all products. The mean proportion of Tscm, Tem, and Tcm cells in the CD3+CAR+ T cell subsets of all products was 23.3% (range: 3.5545.3%), 33.2% (range: 17.267.9%), and 36.1% (range: 20.758.1%), respectively (Fig. S5B). F-CAR-T products exerted significant IFN- release and cytotoxic effects against the CD19+ cell line HELA-CD19 (Fig. S5, C, D).

All 25 infused patients experienced adverse events (AEs) of any grade, with 25 (100%) experiencing grade 3 or higher adverse events. No grade 5 events related to F-CAR-T treatment were observed (Table 2).

CRS occurred in 24 (96%) patients with 18 (72%) grade 12 CRS,6 (24%) of grade 3, and no grade 4 or higher CRS (Fig. S6). In the >14 years old group, 16/20 (80%) patients developed mild CRS, and only 2/20 (10%) developed grade 3 CRS. For 14 years old patients, 2/5 (40%) had mild CRS, yet 3/5 (60%) experienced grade 3 CRS (Table S4). ICANS was observed in 7 (28%) patients, with 2 (8%) grade 3 ICANS occurring in patients >14 years old and 5 (20%) grade 4 ICANS all occurring in patients 14 years old. No grade 5 ICANS was developed (Fig. S7 and Table S4). The most frequent presentation of CRS was fever, particularly a high fever of >39C. The first onset of CRS symptoms occurred between day 3 and 8 post-CAR-T infusion with a median onset at day 4 (range: 110 days). The most common symptoms of ICANS were seizure (5/7) and depressed consciousness (5/7). The median time to ICANS onset from CAR-T cell infusion was 7 days (range: 58), and the median time to resolution was 2 days (Fig. S7). All CRS and ICANS events were managed including early intervention when fever of 39C persisted for 24h. Sixteen (64%) patients received tocilizumab with a median total dose of 160mg (range: 160320mg). Twenty-one (84%) patients received corticosteroids including dexamethasone (median total dose, 43mg; range: 4127mg) and or methylprednisolone (median total dose, 190mg; range: 401070mg). The vast majority of these patients discontinued corticosteroids within 2 weeks. The change in IL-6, IFN-, IL-10, and GM-CSF levels after infusion are selectively shown in Fig. S8. The peak levels of these four cytokines were observed between day 710. Among all 21 cytokines examined, only post-infusion IL-6 levels were associated with moderate to severe CRS and/or ICANS (Figs. S9 and S10).

Superior in vivo proliferation and persistence of F-CAR-T compared to C-CAR-T cells were observed regardless of dose levels. The median peak level was reached on day 10 (range: 714 days) with 1.9105 transgene copies/g of genomic DNA (range: 0.225.2105 transgene copies/g of genomic DNA) by qPCR and 83 F-CAR-T cells per l blood (range: 42102 F-CAR-T cells per l blood) by FCM (Fig. 3A, B). No significant differences were observed among the different dose groups in the mean F-CAR-T copies peak (Fig. 3C). Importantly, there was no significant difference in the mean F-CAR-T copies peak between patients who received corticosteroids compared to those who did not (Fig. 3D).

A F-CAR-T cells in peripheral blood by qPCR. Purple, dose level 1; black, dose level 2; blue, dose level 3; red, dose level 4; B F-CAR-T cells in peripheral blood by flow cytometry. Purple, dose level 1; black, dose level 2; blue, dose level 3; red, dose level 4; C Comparison of the mean peak copy number of F-CAR-T cells in peripheral blood at each dose level. Statistical significance was determined by the MannWhitney test. D Comparison of the mean peak copy number of F-CAR-T cells in peripheral blood with or without steroids. Statistical significance was determined by the MannWhitney test.

Fourteen days after F-CAR-T cell infusion, all patients achieved morphologic CR including 2/25 with CR and 23/25 CR with incomplete hematologic recovery (CRi), which further improved to 11/25 CR and 14/25 CRi 28 days post F-CAR-T (Table 1 and Fig. 4). More importantly, 23/25 (92%) had the minimal residual disease (MRD)-negative remission on day 14 and day 28 after F-CAR-T treatment. Patients achieving remission through CAR-T were given the option to proceed to allo-HSCT. With a median time of 54 days (range: 4581 days) post F-CAR-T infusion, 20 of 23 patients with MRD-negative status decided to pursue consolidative allo-HSCT including one patient who received a 2nd transplant. As of 18 October 2021, with a median follow-up duration of 693 days (range: 84973 days) among the 20 patients who had received allo-HSCT, one patient relapsed on day 172 and died 3 months after relapse, and four patients died from transplant-related mortality (TRM) including infection (n=3) and chronic GVHD (n=1) on day 84, day 215, day 220, and day 312, respectively. The other 15 patients remained in MRD-negative CR with a median remission duration of 734 days (range: 208973) except for one who became MRD-positive on day 294 with CD19+ disease. Among the other three patients (F05, F06, F16), one remained in MRD-negative CR on day 304, one remained in MRD-negative CR until day 303, received allo-HSCT but died from an infection on day 505, and one was lost to follow-up after day 114. Two patients who had MRD-positive CR after infusion withdrew from the study on day 42 and day 44, respectively, to seek other studies.

Clinical outcomes and consolidative allo-HSCT for the 25 patients who were treated with F-CAR-T therapy are shown. On day 28, 23/25 patients achieved MRD-negative CR/CRi. With a median time of 54 days (range: 4581) post F-CAR-T infusion, 20 of 23 patients with MRD-negative status received consolidative allo-HSCT. Among the 20 patients, 1 patient (F23) relapsed on day 172 and died 3 months after relapse. Four patients (F04, F09, F11, F12) died from transplant-related mortality (TRM) including infection (n=3) and chronic GVHD (n=1) on day 84, day 215, day 220, and day 312, respectively. The remaining 15 patients were in MRD-negative CR except for one (F18) who became MRD-positive on day 294. Among the other 3 patients (F05, F06, F16), 1 remained MRD-negative CR on day 304, 1 remained in MRD-negative CR until day 303, received allo-HSCT, and subsequently died from an infection on day 505. One patient was lost to follow-up after day 114. MRD minimal residual disease, CR complete remission, Allo-HSCT allogeneic hematopoietic stem cell transplantation.

F-CAR-T/T ratio in cerebrospinal fluid (CSF) was evaluated by FCM in 13/25 patients with available samples (Table S5). Between days 10 and 32, 9 patients were found to have considerable F-CAR-T penetration in their CSF, ranging from 40.65 to 79.2%, including 4 who developed severe ICANS. Among the other 4 patients, F-CAR-T cell abundance in the CSF ranged from 1.29% to 3.57%, and none experienced severe ICANS. Patients with higher levels of CAR-T in PB on day 10 consistently had higher levels of CAR-T in CSF with the exception of patient F15. Notably, CAR-T cells were still detectable in the CSF on day 101 with a 2.36% CAR-T/T ratio in patient F06, who also had undetectable circulating CAR-T cells at the same time.

In addition, concentrations of seven cytokines (IL-1b, IL-6, IL-10, IFN-, TNF-, MCP-1, and GM-CSF) in CSF samples from the above 10 of 13 patients were measured. Specifically, IL-1b was not detected in any of the 10 patients, and only one patient had detectable GM-CSF. For the other five cytokines, patients with severe ICANS had higher IL-6 levels in contrast to patients without severe ICANS, and the difference between the median level of IL-6 among these two groups of patients was statistically significant (Fig. S11). We did not observe significant differences among the other 4 cytokines between the two groups of patients. No clear relation between the CSF cytokine levels and the F-CAR-T/T % was observed.

Continued here:
Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study | Blood Cancer Journal...

Bone Marrow Stem Cells Comments Off on Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study | Blood Cancer Journal… | July 8th, 2022

REDWOOD CITY, Calif., June 07, 2022 (GLOBE NEWSWIRE) -- Jasper Therapeutics, Inc. ( JSPR), a biotechnology company focused on enabling cures with stem cell therapies, today announced that the Company is participating in the William Blair 42nd Annual Growth Stock Conference, to be held in Chicago from June 6-9, 2022.

Ronald Martell, Jaspers Chief Executive Officer, is scheduled to present on Thursday, June 9th at 8:00AM CT, with a breakout session to follow at 8:40AM CT. A live webcast of the presentation will be available at https://wsw.com/webcast/blair66/jasp/1933236 and at the Companys Investor Events webpage.

About Jasper TherapeuticsJasper Therapeutics, Inc. 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, and potentially curative, allogeneic hematopoietic cell transplants and gene therapies. A clinical study of JSP191 as a novel, disease-modifying, therapeutic for patients with lower risk MDS is also planned to begin in 2022. In parallel, Jasper Therapeutics, Inc. is advancing its preclinical mRNA hematopoietic stem cell grafts 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 StatementsCertain 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 regarding the potential of the Companys JSP191 and mRNA engineered stem cell graft programs. These statements are based on various assumptions, whether or not identified in this press release, and on the current expectations of Jasper 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. These forward-looking statements are subject to a number of risks and uncertainties, including general economic, political and business conditions; the risk that the potential product candidates that Jasper 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 Jaspers product candidates; the risk that prior study results may not be replicated; 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 will be unable to successfully market or gain market acceptance of its product candidates; the risk that Jaspers product candidates may not be beneficial to patients or successfully commercialized; patients willingness to try new therapies and the willingness of physicians to prescribe these therapies; the effects of competition on Jaspers business; the risk that third parties on which Jasper depends for laboratory, clinical development, manufacturing and other critical services will fail to perform satisfactorily; the risk that Jaspers 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 will be unable to obtain and maintain sufficient intellectual property protection for its investigational products or will infringe the intellectual property protection of others; and other risks and uncertainties indicated from time to time in Jaspers filings with the SEC. If any of these risks materialize or Jaspers assumptions prove incorrect, actual results could differ materially from the results implied by these forward-looking statements. While Jasper may elect to update these forward-looking statements at some point in the future, Jasper specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Jaspers 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 Advisors617-429-3548[emailprotected]

Jeet Mahal (investors)Jasper Therapeutics650-549-1403[emailprotected]

Read the original post:
Jasper Therapeutics to Participate in the William Blair 42nd Annual Growth Stock Conference - GuruFocus.com

Bone Marrow Stem Cells Comments Off on Jasper Therapeutics to Participate in the William Blair 42nd Annual Growth Stock Conference – GuruFocus.com | July 8th, 2022

The very thought of getting someone elses poop transfused in your body may make you cringe but stool transplant has not only helped patients with gastrointestinal tract issues, it has also saved those who have had bone marrow transplants.

At Deenanath Mangeshkar Hospitals Centre of Excellence in Infectious Diseases and Department of Haematology, Pune, seven of the 11 patients of bone marrow transplants developed Clostridium difficile infection. They were treated with faecal microbial transplant (FMT), also referred to as stool transplant, over the past year.

Research worldwide has shown that a faecal transplant can restore healthy bacteria in the lower intestine which can help control Clostridium difficile or C. diff. According to the Johns Hopkins University School of Medicine, FMT can be more effective than antibiotics for keeping C. diff in check in some cases.

Since C. diff infection can recur and cause colitis (inflammation in the colon), FMT restores good and healthy bacteria, said Dr Parikshit Prayag, infectious disease consultant and in-charge of the Centre of Excellence in Infectious Diseases at Deenanath Mangeshkar hospital.

Dr Sameer Melinkeri, head of the department of haemotology at the hospital, said C. diff infection-related diarrhoea can occur in a normal setting in which antibiotics can be used for treatment. However, antibiotic treatment for recurrent infections can involve one or more courses of medication and their effectiveness comes down with each subsequent bout. FMT can arrest such infections post bone marrow transplant as it can be life-threatening, he added.

FMT is also done for certain disease conditions like Graft vs host disease (GvHD). Most people who undergo a bone marrow transplant suffer from blood cancer. Graft vs host disease can occur at any time after an allogeneic transplant where the donated bone marrow or peripheral stem cells can attack the recipients body. It can develop in the GI tract, skin or liver, Dr Prayag said.

Latest research published in the Journal of International Medical Research and others has shown how FMT is a promising treatment for patients with steroid-resistant GvHD. We have seen clinically relevant results in six of our patients, Dr Prayag said.

So, who can be donors? They are selected based on certain parameters. They should not be immune-compromised or have taken antibiotics over the past six months, says Dr Sampada Patwardhan, head of the department of microbiology at the hospital. Donor screening has to be done carefully. We need to rule out infections, she said.

Procedures on the transplant delivery methods may vary like colonoscopy and use of nasojejunal tube. The recovery may take a week or more and in most cases there are at least two weekly installations of the stool (in liquid form).

Very few centres conduct FMT and among them, the centre at Deenanath Hospital actively treats cases involving bone marrow transplants. At a recent virtual meeting of the International Society of Blood Transfusion, Dr Prayag made a strong case for encouraging stool transplants. The condition of C. diff is also underdiagnosed in the country as there isnt adequate infrastructure to correctly detect the problem, he pointed out.

In fact, FMT is being touted as a treatment option for many gut health issues. In an opinion article published on June 30 in the journal Trends in Molecular Medicine, a team from Harvard Medical School and Brigham and Womens Hospital (BWH) proposes that individuals bank samples of their own gut microbiota when they are young and healthy for potential use later in life in an autologous FMT.

A report in Science Daily quotes corresponding author Yang-Yu Liu, an associate professor of medicine at Harvard and an associate scientist in the Channing Division of Network Medicine at BWH, as saying, The idea of rewilding the human microbiome has taken off in recent years and has been hotly debated from medical, ethical and evolutionary perspectives. It is still unknown if people in industrialized societies can gain some health benefit by restoring their microbiome to an ancestral state. In this paper, we proposed a way to rejuvenate the human gut microbiome.

The report also listed OpenBiome, a non-profit stool bank based in Somerville, Massachusetts, as the first stool bank to offer an option for individuals to bank their own stool for future treatment of C. diff infection. Yang and his colleagues are now looking at if this treatment can be used for other diseases.

Conceptually, the idea of stool banking for autologous FMT is similar to when parents bank their babys cord blood for possible future use. However, there is greater potential for stool banking, and we anticipate that the chance of using stool samples is much higher than for cord blood. But there are many practical issues to implementing this idea, Yang is quoted as saying, hinting at optimal storage and cryopreservation issues.

See more here:
Cutting Edge: Poop therapy can save your gut, and your life - The Indian Express

Bone Marrow Stem Cells Comments Off on Cutting Edge: Poop therapy can save your gut, and your life – The Indian Express | July 8th, 2022

Ulcerative colitis, or UC, is a form of inflammatory bowel disease characterized by chronic and relapsing large intestine inflammation. Genetics account for only a minority of UC cases; hence, to develop treatments, researchers need to understand better the environmental contributions to this condition.

Gut microbes are in perpetual contact with the gastrointestinal tract, so they comprise important but poorly defined environmental variables contributing to UC development. Many studies have reported changes in gut microbiome composition in patients with UC compared to healthy individuals. While that suggests a potential role for gut microbes in UC pathogenesis, researchers have yet to pinpoint the causative microbes and associated bacterial proteins.

Dennis Wolans lab at Scripps Research is interested in identifying small-molecule activators and inhibiting bacterial enzymes involved in proliferation of human disease. Wolan said he was curious about what bacterial enzymes of the microbiome contribute to UC development.

Many publications have focused on the role of the microbiome in both health and disease states, he said. Most of these were focused on the taxonomical and phylogenic differences in the microbiome. But what about the associated bacterial proteins? What proteins are these gut bacteria making in disease conditions, and how are these interacting with the human body?

One protein of interest was serine proteases, a type of proteolytic enzyme that cleaves peptides at the serine amino acid. Researchers long have recognized that they coordinate many physiological processes and play key roles in regulating the inflammatory response. Previous studies have suggested increased proteolytic activity in microbial samples harvested from people with inflammatory disorders such as UC and Crohns disease.

Peter ThuyBuon, a graduate student and later a postdoc in the Wolan lab, led a project to study differential protein expression in healthy and UC fecal samples. He and the team described the project in a recent paper in the journal Molecular & Cellular Proteomics. In addition to standard mass spectrometry, ThuyBuon used a small molecular approach called affinity-based proteomic profiling to target and enrich for different types of proteases in the fecal samples.

We showed that there were 176 discrete host and microbial protein groups differentially enriched between healthy and UC patients, Wolan said. Furthermore, further enrichment of these proteins showed significantly higher levels of serine proteases in UC patients.

This finding has inspired exciting future research questions. For example, are elevated serine proteases the driver of UC or merely the effect of UC disease progression?

There is a lot of exciting work to be done using these findings, Wolan said. Future molecular studies should focus on how serine proteases might be contributing to UC and whether their levels can be manipulated to modify disease progression.

Functional proteomics has shown the potential role of serine proteases in UC. Future steps will include drug discovery and design of small-molecule regulators of bacterial enzymes.

Wolan said, Ultimately, the moderation of microbiome distribution in UC via external small-molecule intervention can serve as a foundation for UC prevention and treatment.

Visit link:
Proteases implicated in ulcerative colitis - ASBMB Today

Bone Marrow Stem Cells Comments Off on Proteases implicated in ulcerative colitis – ASBMB Today | July 8th, 2022

Clusters of the earliest hematopoietic cells being born in the walls of the umbilical artery of a mouse embryo. The cells colored in red represent embryonic multipotent progenitor cells (eMPPs). Credit: Sachin H. Patel/Boston Childrens Hospital

Barcoding studies discovered two independent sources for blood cells in mice. If confirmed in humans, our understanding of blood cancers, bone marrow transplants, and the aging immune system will change.

The origins of our blood may not be quite what we thought. Using cellular barcoding in mice, groundbreaking research finds that blood cells originate not from one type of mother cell, but two, with potential implications for blood cancers, bone marrow transplant, and immunology. Fernando Camargo, PhD, of the Stem Cell Program at Boston Childrens Hospital led the study, published in the journal Nature on June 15, 2022.

Historically, people have believed that most of our blood comes from a very small number of cells that eventually become blood stem cells, also known as hematopoietic stem cells, says Camargo, who is also a member of the Harvard Stem Cell Institute and a professor at Harvard University. We were surprised to find another group of progenitor cells that do not come from stem cells. They make most of the blood in fetal life until young adulthood, and then gradually start decreasing.

The researchers are now following up to see if the findings also apply to humans. If so, these cells, known as embryonic multipotent progenitor cells (eMPPs), could potentially inform new treatments for boosting aging peoples immune systems. They could also shed new light on blood cancers, especially those in children, and help make bone marrow transplants more effective.

Camargos team applied a barcoding technique they developed several years ago. Using either an enzyme known as transposase or CRISPR gene editing, they inserted unique genetic sequences into embryonic mouse cells in such a way that all the cells descended from them also carried those sequences. This enabled the team to track the emergence of all the different types of blood cells and where they came from, all the way to adulthood.

Previously, people didnt have these tools, says Camargo. Also, the idea that stem cells give rise to all the blood cells was so embedded in the field that no one attempted to question it. By tracking what happened in mice over time, we were able to see new biology.

Through barcoding, the researchers found that eMPPs, as compared with blood stem cells, are a more abundant source of most lymphoid cells important to the immune responses, such as B cells and T cells. Camargo believes the decrease in eMPPs that they observed with age may explain why peoples immunity weakens as they get older.

Were now trying to understand why these cells peter out in middle age, which could potentially allow us to manipulate them with the goal of rejuvenating the immune system, says Camargo.

In theory, there could be two approaches: extending the life of eMPP cells, perhaps through growth factors or immune signaling molecules, or treating blood stem cells with gene therapy or other approaches to make them more like eMPPs.

Camargo is also excited about the potential implications for better understanding and treating blood cancers. For example, myeloid leukemias, striking mostly older people, affect myeloid blood cells such as granulocytes and monocytes. Camargo thinks these leukemias may originate from blood stem cells, and that leukemias in children, which are mostly lymphoid leukemias, may originate from eMPPs.

We are following up to try to understand the consequences of mutations that lead to leukemia by looking at their effects in both blood stem cells and eMPPs in mice, he says. We want to see if the leukemias that arise from these different cells of origin are different lymphoid-like or myeloid-like.

Finally, the recognition that there are two types of mother cells in the blood could revolutionize bone marrow transplant.

When we tried to do bone marrow transplants in mice, we found that the eMPPs didnt engraft well; they only lasted a few weeks, says Camargo. If we could add a few genes to get eMPPs to engraft long term, they could potentially be a better source for a bone marrow transplant. They are more common in younger marrow donors than blood stem cells, and they are primed to produce lymphoid cells, which could lead to better reconstitution of the immune system and fewer infection complications after the graft.

Reference: Lifelong multilineage contribution by embryonic-born blood progenitors by Sachin H. Patel, Constantina Christodoulou, Caleb Weinreb, Qi Yu, Edroaldo Lummertz da Rocha, Brian J. Pepe-Mooney, Sarah Bowling, Li Li, Fernando G. Osorio, George Q. Daley and Fernando D. Camargo, 15 June 2022, Nature.DOI: 10.1038/s41586-022-04804-z

Sachin H. Patel, MD, PhD, of the Stem Cell Program (now at University of California San Francisco) and Constantina Christodoulou, PhD (now at Bristol Myers Squibb) were co-first authors on the paper. The study was funded by the National Institutes of Health (HL128850-01A1, P01HL13147), the Evans MDS Foundation, the Alex Lemonade Foundation, the Leukemia and Lymphoma Society, and the Howard Hughes Medical Institute. The authors declare no competing interests.

See the article here:
The Origins of Our Blood May Not Be What We Thought - SciTechDaily

Bone Marrow Stem Cells Comments Off on The Origins of Our Blood May Not Be What We Thought – SciTechDaily | June 30th, 2022

Srinagar, June 29: In a recent case, doctors at HCMCT Manipal Hospitals, Dwarka successfully treated a 9-year-old patient from Iraq who was suffering from a rare disease called Diamond Blackfan anemia presenting as aplastic anaemia.

She presented with low hemoglobin, low platelets, and low TLC. The team led by Dr. Divya Bansal successfully performed a bone marrow transplant where the donor was the patients 3-year-old sister.

Diamond-Blackfan anemia (DBA) is a rare blood disorder that occurs when the bone marrow fails to make red blood cells, which are essential for carrying oxygen from the lungs to all the other parts of the body. In this case, the patient had a extremely rare presentation of Diamond Blackfan anemia, where her bone marrow was suppressed and she had low hemoglobin, platelets, and TLC.

This was a challenging case as she was platelet transfusion refractory; no matter how many platelets she was given, her platelet count did not rise, and she was bleeding profusely from the nose and mouth, which was life threatening. Transplant in this condition was particularly challenging, as conditioning therapy, which is given before donor stem cell infusion, further depletes the platelets.

Speaking about this case, Dr. Divya Bansal, Consultant of Clinical Hematology and Bone Marrow Transplant, HCMCT Manipal Hospital, Dwarka said, "This was a different case, the little girl was brought to us with a history of weakness and bleeding from the nose and mouth. We evaluated her further and found that she had congenital bone marrow failure syndrome, diamond blackfan anemia. There was a high PNH clone (paroxysmal nocturnal hemoglobinuria), which is another uncommon condition in the general population and even more so in children. She had a congenital cause as well as an acquired cause for aplastic anemia. Luckily, one of her sisters, who was just 3 years old, turned out to be a 100% HLA match for a bone marrow transplant. However, the difference between donor weight and recipient weight was very wide. The recipient was around 40 kg, and the donor was around 12 kg. Generally, a 10% weight difference is accepted. The protocol is that when you have a major weight difference, then the stem cell collection is done in two settings. But due to the time factor, we had to do it in one sitting only."

The patient contracted a dreadful infection at an early stage of the transplant. However, with the assistance of experienced experts and cutting-edge technology at Manipal Hospitals, the patient was successfully treated, and she was engrafted on day 14 of the transplant, and the chimerism was performed on the 30th day. She is now 100 percent donor chimerism, which means that all the cells in her body are from the donor. This was a success story for us because it was a rare disease with exceedingly rare complications and presentation but was done successfully.

More:
9-year-old Iraqi girl diagnosed with rare blood disorder successfully treated at HCMCT Manipal Hospitals - Rising Kashmir

Bone Marrow Stem Cells Comments Off on 9-year-old Iraqi girl diagnosed with rare blood disorder successfully treated at HCMCT Manipal Hospitals – Rising Kashmir | June 30th, 2022

An estimated 1,240,000 blood cancer cases emerge annually worldwide, accounting for approximately 6 per cent of all the cancer cases. Meanwhile 720,000 people die of blood cancer every year, accounting for 7 per cent of the cancer deaths.

These statistics were shared by Dr Munira Borhany, haematologist and associate professor at the National Institute of Blood Diseases & Bone Marrow Transplant (NIBD) at a public awareness seminar held recently in collaboration with the Neurospinal & Cancer Care Postgraduate Institute.

The event was titled Rising Burden of Blood Cancers in Pakistan.

"Cancers of blood, bone marrow and lymphatic system are collectively referred to as blood cancers ranging from slow-growing to very aggressive. When the body's red blood cells, white blood cells or platelet production is unusual or abnormal, blood cancer develops. It normally begins in the bone marrow, which is responsible for the production of blood. The normal functioning, growth and development of blood cells that fight infection and make healthy blood cells are disrupted by this type of cancer. There are 137 types of blood cancers and related disorders, she explained, adding that blood cancer was among the most common form of cancers to affect children and adolescents.

The haematologist said that the symptoms of blood cancer could be quite variable depending upon its type. The common symptoms included unexplained fatigue, fever, weakness, and tiredness which could be fast develop in conditions such as acute leukaemia. There may be bleeding manifestations, bone pains, occurrence of swellings in the entire body, loss of appetite, weight loss and abdominal pain, she added.

She said that in general, the symptoms could be quite non-specific such as flu-like symptoms to more dramatic ones such as bleeding manifestations and severe infection. Highlighting the efficacy of bone marrow transplant (BMT) for such patients, she said the BMT was a highly effective therapy and often the only hope for a cure or a longer life for patients with blood cancers.

Dr Munira explained BMT was a procedure to replace disordered bone marrow with healthy bone marrow stem cells. Transplant physicians use this procedure to eliminate cancer or defective stem cells and restore a patient's blood and immune systems.

She added that not all patients with blood cancer required BMT. The need for a bone marrow transplant is evaluated case-wise based on the individual patientss underlying diagnosis, treatment response and disease genetic profile. She informed the event that patients' response to treatment in cases of acute leukemia had improved, due to the cutting-edge genetic profiling technologies combined with innovative medication.

Highlighting the benefits of BMT, Dr Munira said the procedure had two major advantages over other forms of transplants firstly, the donors did not lose any vital part of their body for life and secondly, the recipients had to take the immunosuppressive drug only for nine months.

The bone marrow transplant unit at the NIBD has successfully performed 750 BMT, including 690 allogeneic and 60 autologous blood stem cell transplants with the success rate of more than 80 per cent despite the pressure placed on the healthcare system due to Covid-19 pandemic as well as national economic crisis and escalation of the dollar value against the rupee, she said.

The expert said a bone marrow transplant surgery cost more than Rs4 million in Pakistan but the entire procedure was performed at the NIBD free of charge. She requested the industrial sector, philanthropists and NGOs to support the NIBD for this noble cause.

Blood cancer treatment success rates are improving drastically, and patients are living longer than ever before. There are now various effective and targeted therapeutic agents that have been effective such as chemotherapy, radiotherapy, targeted therapy, bone marrow transplantation and immunotherapy in beating cancer. There is a better chance of a complete cure with early diagnosis, she maintained.

Earlier, NIBD Chief Executive Officer Usama Sultan Shamsi told the seminar that there was a need for increasing awareness among the public as well as medical fraternity to help realise that blood cancer and related disorders were just another forms of disease with a potential for high cure rates provided that they were investigated properly and specific treatment instituted.

More here:
Success rate of blood cancer treatment drastically improving, seminar told - The News International

Bone Marrow Stem Cells Comments Off on Success rate of blood cancer treatment drastically improving, seminar told – The News International | June 20th, 2022

First prospective controlled trial in the world on treating chronic back pain with stem cells shows 70% of participants helped by the treatment

Dr. Sairam Atluri has successfully treated more than 400 patients at his StemCures clinic in Cincinnati over the past five years

Proper use of bone marrow mesenchymal stem cells, or BM-MSCs, for chronic pain treatment follows FDA protocols

CINCINNATI, June 15, 2022 /PRNewswire/ --Local Cincinnati pain physician Dr. Sairam Atluri led the first prospective controlled clinical trial on using bone marrow mesenchymal stem cells (BM-MSCs) for chronic pain. 70% of study participants gained significant pain relief and improved physical and mental function. The first of its kind in the world, the study was completed last month in Ohio.

"Evaluation of the Effectiveness of Autologous Bone Marrow Mesenchymal Stem Cells in the Treatment of Chronic Low Back Pain Due to Severe Lumbar Spinal Degeneration: A 12-Month, Open-Label, Prospective Controlled Trial"was published in the official publication of the American Society of Interventional Pain Physicians, Pain Physician Journal. It is the only scientifically accepted controlled study in the world. 15 other physicians participated in the study.

"When I saw the results my patients were getting at my StemCures health facility, I and my colleagues decided the only way to get physicians to accept this treatment as a mainstream therapeutic for chronic pain was to get a study published in a respected journal," said Dr. Atluri. "About 90 percent of physicians have little to no knowledge of this treatment. They, and their patients, need to know."

40 patients were in the BM-MSC treatment group for the study, and 40 were in a control group, receiving traditional pain modalities such as injections, physical therapy, nerve ablations, and pain medications. The research group then followed their progress for one year:

Almost 70% of those receiving BM-MSCs had significant pain relief and improved physical and mental function. All had cut down or eliminated their pain medication.

Only 8% in the controlled group (not receiving BM-MSCs) had any improved functioning.

Story continues

BM-MSC treatment is a constructive pain therapeutic, as the patient's own cells, that are proven to be safe and effective, are extracted and then injected back into the area that needs repair and healing. The painless procedure takes about 90 minutes and is typically performed just one time for each area affected by chronic pain.

According to Dr. Atluri, it's important the public knows what BM-MSCs are, and what they aren't.

Mesenchymal stem cells are designed to repair and heal. They are present in every tissue, ready to spring into action if you cut your finger, or suffer an acute muscle injury.

BM-MSC treatment, done properly, follows allowed FDA protocols.

BM-MSCs are not embryonic or fetal stem cells. There are almost no cell therapies currently performed with these cell types.

These are not amniotic stem cells. This is important because there are many "pseudo clinics" advertising stem cell procedures that use "off-the-shelf" amniotic stem cells. Most are not performed by qualified physicians, are violating FDA protocols, and are a waste of money. They may also adversely affect your health.

BM-MSCs are not hematopoietic stem cells derived from blood platelets for treatments such as leukemia.

Dr. Atluri, who has successfully treated over 400 patients over the last five years at his clinic, also pointed out that by making the treatment more accessible to chronic pain sufferers, more patients can wean themselves off prescription painkillers. The consequences of that could significantly impact this country's opioid addiction problem.

"These results of this treatment are astonishing and now, irrefutable," said Dr. Atluri. "I travel around the world educating and teaching other physicians about BM-MSCs and now I can do it with scientific proof in hand. Every physician treating chronic pain patients should be identifying their BM-MSC candidates, which are those who suffer from arthritis or joint degeneration for more than six months and don't have contraindications such as cancer.

"It's changing people's lives and in many cases, giving them a future to look forward to for the first time in years."

For more information about the study and bone marrow mesenchymal stem cells treatment, contact Dr. Atluri at hisStemCures clinic at 513-624-7525. The clinic address is 7655 Five Mile Rd., Ste. 117, Cincinnati.

Cision

View original content:https://www.prnewswire.com/news-releases/cincinnati-pain-management-physician-leads-first-successful-stem-cell-controlled-trial-with-70-of-participants-seeing-positive-results-301568002.html

SOURCE Dr. Sairam Atluri

Link:
Cincinnati Pain Management Physician Leads First Successful Stem Cell Controlled Trial with 70% of Participants Seeing Positive Results - Yahoo...

Bone Marrow Stem Cells Comments Off on Cincinnati Pain Management Physician Leads First Successful Stem Cell Controlled Trial with 70% of Participants Seeing Positive Results – Yahoo… | June 20th, 2022

Symptoms of the disease are usually visible at the age of 5 months and change over time. Some of the common symptoms include pain, anaemia, frequent infections, swelling of hands and feet and vision problem

Sickle-shaped cells and normal blood cells in human blood. Image courtesy: Wikimedia Commons/Dr Graham Beards

World Sickle Cell Day is marked every year on 19 June with an aim to raise awareness about sickle cell disease. Sickle Cell Disease is a group of disorders that impact haemoglobin, the molecule in red blood cells which deliver oxygen to cells throughout the body.

Individuals who live with this disease have haemoglobin S, an atypical haemoglobin molecule which distorts red blood cells into a sickle or a crescent shape. The disease is usually transmitted from parents to children.

What are the symptoms?

Symptoms of the disease are usually visible at the age of 5 months and change over time. Some of the common symptoms include pain, anaemia, frequent infections, swelling of hands and feet and vision problem.

What are the different types of Sickle Cell Disease?

If one of the parents has a problem gene, then the child will not have symptoms but will possess sickle cell trait.

What is the treatment?

The disease can be detected in an infant during the screening process of a newborn. In case, there is a family history of the Sickle Cell disease, it can even be diagnosed at the time of pregnancy.

The only way to cure it is either stem cell or a bone marrow transplant. The symptoms can also be dealt with the use of antibiotics, periodic blood transfusion, pain killers, and vaccinations.

Read all the Latest News, Trending News,Cricket News, Bollywood News,India News and Entertainment News here. Follow us on Facebook, Twitter and Instagram.

Read more:
World Sickle Cell Day 2022: Know all about symptoms and treatment of the disease - Firstpost

Bone Marrow Stem Cells Comments Off on World Sickle Cell Day 2022: Know all about symptoms and treatment of the disease – Firstpost | June 20th, 2022

-- First Site Will Enroll First Patient in the Clinical Study--

MELVILLE, NY., June 13, 2022 (GLOBE NEWSWIRE) -- BioRestorative Therapies, Inc. (the Company or BioRestorative) (NASDAQ: BRTX), a clinical stage company focused on stem cell-based therapies, today announced site initiation for its Phase 2 clinical trial targeting chronic lumbar disc disease (cLDD). The Denver Spine and Pain Institute is the first clinical site to be initiated. Additional selected sites are expected to be initiated in 2022.

BioRestoratives Phase 2 trial is a double-blind controlled, randomized study to evaluate the safety and preliminary efficacy of a single dose intradiscal injection of the Companys autologous investigational stem cell-based therapeutic, BRTX-100. A total of up to 99 eligible patients will be randomized at up to 15 centers in the United States to receive either the investigational drug (BRTX-100) or control in a 2:1 fashion.

Currently there are no approved, cell-based therapies for cLDD. While there is encouraging data that suggests that patients with cLDD could benefit from autologous stem cell transplants, the low oxygen micro-environment of the disc makes cell-based therapies challenging. BRTX-100 is manufactured under low oxygen conditions and engineered to survive this environment, said Scott Bainbridge, M.D., Principal Investigator for the BRTX-100 trial at The Denver Spine and Pain Institute. Positive proof-of-concept data in this trial could be disruptive and support the potential applicability of BRTX-100 to other spine and musculoskeletal disorders where low oxygen micro-environments are found.

We are pleased to initiate the first of several sites across the United States that will be enrolling for the trial, said Lance Alstodt, Chief Executive Officer of BioRestorative Therapies. Our sites have been carefully reviewed and selected and have clinical expertise in treating patients who could potentially benefit from BRTX-100. We look forward to working with the principal investigators and their clinical trial teams.

About BioRestorative Therapies, Inc.

BioRestorative Therapies, Inc. (www.biorestorative.com) develops therapeutic products using cell and tissue protocols, primarily involving adult stem cells. Our two core programs, as described below, relate to the treatment of disc/spine disease and metabolic disorders:

Forward-Looking Statements

This press release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. You are cautioned that such statements are subject to a multitude of risks and uncertainties that could cause future circumstances, events or results to differ materially from those projected in the forward-looking statements as a result of various factors and other risks, including, without limitation, those set forth in the Company's latest Form 10-K filed with the Securities and Exchange Commission and other public filings. You should consider these factors in evaluating the forward-looking statements included herein, and not place undue reliance on such statements. The forward-looking statements in this release are made as of the date hereof and the Company undertakes no obligation to update such statements.

CONTACT:Email: ir@biorestorative.com

Read this article:
BioRestorative Therapies Announces Clinical Site Initiation for the Company's Phase 2 Clinical Trial to Treat Chronic Lumbar Disc Disease (cLDD) -...

Bone Marrow Stem Cells Comments Off on BioRestorative Therapies Announces Clinical Site Initiation for the Company’s Phase 2 Clinical Trial to Treat Chronic Lumbar Disc Disease (cLDD) -… | June 20th, 2022

MarketQuest.biz has announced the addition of new research titled Global Rheumatoid Arthritis Stem Cell Therapy Market from 2022 to 2028, which encompasses regional and global market data and is predicted to generate attractive valuation.The Rheumatoid Arthritis Stem Cell Therapy research covers market drivers, opportunities, limiting factors, and barriers. It provides a quantitative market study based on annual reports, product literature, industry announcements, and other sources.

The report explains the market definition, classifications, applications, engagements, and global Rheumatoid Arthritis Stem Cell Therapy industry trends are.It gives a realistic picture of the current market position incorporating original and predicted market estimates.The report gives a thorough analysis of their product portfolios to investigate the products and applications they focus on while working in the worldwide Rheumatoid Arthritis Stem Cell Therapy market. The report offers valuable suggestions to new just as set up players of the market.

DOWNLOAD FREE SAMPLE REPORT: https://www.marketquest.biz/sample-request/121261

In order to improve industrial planning, data points such as flow patterns, openings, drivers, limits, and statistics are acquired from trusted sources. The data and numbers in the research report have been provided comprehensively, using graphical and pictorial representations to understand the market better.Further when datais synthesised, statistical analysis takes place. Several processes, including screening, integration, and data extrapolation, must be performed prior to data validation.

The product types covered in the report include:

The application types covered in the report include:

The countries covered in the market report are:

The key and emerging market players in the global market include:

ACCESS FULL REPORT: https://www.marketquest.biz/report/121261/global-rheumatoid-arthritis-stem-cell-therapy-market-2022-by-company-regions-type-and-application-forecast-to-2028

Significance of The Report gives the idea about thebroad and precise understanding, industry drivers and challenges affecting the industry growth, planning the business strategies and factors leading to the market development, and evaluating the market competition and planning

Customization of the Report:

This report can be customized to meet the clients requirements. Please connect with our sales team (sales@marketquest.biz), who will ensure that you get a report that suits your needs. You can also get in touch with our executives on 1-201-465-4211 to share your research requirements.

Contact UsMark StoneHead of Business DevelopmentPhone: 1-201-465-4211Email: sales@marketquest.biz

Read the rest here:
Global Rheumatoid Arthritis Stem Cell Therapy Market 2022 Swot Analysis by Top Key Vendors, Demand And Forecast Research to 2028 Designer Women -...

Bone Marrow Stem Cells Comments Off on Global Rheumatoid Arthritis Stem Cell Therapy Market 2022 Swot Analysis by Top Key Vendors, Demand And Forecast Research to 2028 Designer Women -… | June 20th, 2022