EDISON, N.J., July 22, 2022 (GLOBE NEWSWIRE) -- Hepion Pharmaceuticals, Inc. (NASDAQ:HEPA), a clinical mid-stage biopharmaceutical company focused on Artificial Intelligence (“AI”)-driven therapeutic drug development for the treatment of non-alcoholic steatohepatitis (“NASH”) and hepatocellular carcinoma (“HCC”), announced today that its 2022 annual meeting of stockholders (the “Annual Meeting”) has been further adjourned to Friday, August 5, 2022 at 9:00 a.m. Eastern Time with respect to Proposal 4 (Authorized Share Increase), as described in Hepion’s definitive proxy statement filed with the U.S. Securities and Exchange Commission (the “SEC”) on April 29, 2022 (the “Proxy Statement”).

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Hepion Pharmaceuticals Announces Further Adjournment of Annual Meeting of Stockholders

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ORLANDO, FL, July 22, 2022 (GLOBE NEWSWIRE) -- Immune Therapeutics, Inc. (OTC Pink: IMUN) (“Immune” or “IMUN”), a specialty pharmaceutical company involved in the acquisition, development and commercialization of pharmaceutical and biotechnology products that have a short and well-defined path to market, is pleased to announce the appointment of Dr. Stephen “Steve” Wilson as Immune’s Chief Executive Officer (CEO), President, and interim Chief Financial Officer (CFO) effective July 19, 2022; he will continue to serve as a member of the Company’s Board of Directors.

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Immune Therapeutics, Inc. Appoints Dr. Stephen Wilson as Chief Executive Officer

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SAN DIEGO, July 22, 2022 (GLOBE NEWSWIRE) -- Revelation Biosciences Inc. (NASDAQ: REVB) (the “Company” or “Revelation”), a clinical-stage life sciences company that is focused on the development of immunologic?based therapies for the prevention and treatment of disease, today announced topline data for its Phase 1b CLEAR clinical study to evaluate the effect of intranasal REVTx-99b on nasal challenge allergen in participants with allergic rhinitis to rye grass pollen.

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Revelation Biosciences Inc. Announces Topline Data for Phase 1b CLEAR Clinical Study of REVTx-99b for the Treatment of Allergic Rhinitis

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HAIFA, Israel, July 25, 2022 (GLOBE NEWSWIRE) -- Pluri Inc. (Nasdaq: PLUR) (TASE: PLUR) (“Pluri” or the “Company”), a leading biotechnology company, today announced its name change (from Pluristem Therapeutics Inc. Nasdaq: PSTI), reflecting a broader strategy of leveraging its 3D cell expansion technology to develop innovative cell-based products that can be harnessed for a range of fields beyond medicine, providing solutions for various areas of the life sciences. As of July 26, 2022, Pluri will begin trading on Nasdaq under the new ticker symbol “PLUR,” CUSIP number 72942G 104.

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Pluristem Therapeutics Inc. Changes its Name to “Pluri Inc.” Reflecting the Company’s Strategy to Leverage its Innovative 3D Cell-based...

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Basel, July 25, 2022 – Sandoz, a global leader in generic and biosimilar medicines, announced today that the US Food and Drug Administration (FDA) has accepted its biologics license application (BLA) for a proposed first-of-a-kind biosimilar natalizumab, developed by Polpharma Biologics.

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Applications for proposed first-of-a-kind multiple sclerosis biosimilar natalizumab accepted by US FDA and EMA

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COPENHAGEN, Denmark, July 25, 2022 – Bavarian Nordic A/S (OMX: BAVA) announced today that the European Commission (EC) has extended the marketing authorization for the Company’s smallpox vaccine, IMVANEX® to include protection from monkeypox and disease caused by vaccinia virus. The approval, which follows a positive opinion by the Committee for Medicinal Products for Human Use (CHMP) on July 22, 2022, is valid in all European Union Member States as well as in Iceland, Liechtenstein, and Norway.

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Bavarian Nordic Receives European Approval of Extension of Vaccine Label to Include Monkeypox

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Global Stem Cell ManufacturingMarket Is Expected To Reach USD 21.71 Billion By 2029 At A CAGR Of 9.1 percent.

Maximize Market Research has published a report on theGlobal Stem Cell Manufacturing Marketthat provides a detailed analysis for the forecast period of 2022 to 2029.

Global Stem Cell ManufacturingMarket Scope:

The report provides comprehensive market insights for industry stakeholders, including an explanation of complicated market data in simple language, the industrys history and present situation, as well as expected market size and trends. The research investigates all industry categories, with an emphasis on key companies such as market leaders, followers, and new entrants. The paper includes a full PESTLE analysis for each country. A thorough picture of the competitive landscape of major competitors in theGlobal Stem Cell Manufacturingmarket by goods and services, revenue, financial situation, portfolio, growth plans, and geographical presence makes the study an investors guide.

Request Free Sample:@https://www.maximizemarketresearch.com/request-sample/73762

Global Stem Cell Manufacturing Market Overview:

Observing stem cells evolve into cells in bones, the circulatory system, nerve cells, and other organs of the body may help scientists understand how illnesses and disorders occur. Stem cells can be programmed to generate particular cells that can be utilized in humans to grow and mend tissues that have been damaged or harmed by sickness. Stem cell therapy may assist people with spinal cord injuries, metabolic disorders, Parkinsons disease, amyotrophic lateral sclerosis, Alzheimers disease, cardiovascular disorders, brain hemorrhage, burns, malignancy, and rheumatoid arthritis. Stem cells can be used to create new tissue for transplant and genetic engineering. Doctors are always learning more about stem cells and how they might be used in transplant and cellular therapies.

Global Stem Cell ManufacturingMarketDynamics:

Stem cells are crucial in illness treatment and specialized research initiatives such as customized therapy and genetic testing. As public and commercial stakeholders throughout the world become more aware of stem cells therapeutic potential and the scarcity of therapeutic approaches for rare illnesses, they are increasingly focusing on the development of stem cell-based technology.

Specialized procedures are required for stem cell separation, refinement, and storage (such as expansion, differentiation, cell culture media preparation, and cryopreservation). Additionally, the production scale-up of stem cell lines and associated items is frequently accompanied by major technological challenges that impede the whole production process and result in large operational expenses. As a result, stem cell products are frequently more expensive than pharmaceutical medications and biopharmaceuticals.

Additionally, the growing popularity of tailored medications is driving the market growth. Scientists are researching novel procurement strategies that can be used to manufacture tailored medications. For example, iPSC treatments are created by taking a little amount of a patients plasma or skin cells and reprogramming them to make new cells and tissue for transplant. As a result, future tailored treatments can be produced using these cells.

Global Stem Cell ManufacturingMarketRegional Insights:

North America (particularly the United States) held the largest market share in 2021, owing to factors such as the availability of significant contenders active in creating stem cell treatments, enhanced medical facilities, significant R&D financial backing available, and favorable initiatives from healthcare organizations, as well as robust reimbursement. Because of government initiatives and serious scientific activity in the country, the United States leads the continentsGlobal Stem Cell Manufacturingmarket.

Healthcare organizations are promoting cellular therapies for rising ailments. Due to higher advancement of stem cell-based treatments, federal actions for creating regenerative medications, the creation of multiple stem cell banks, and the continents increasing clinical studies for genetic manipulation and medical technology, the APACGlobal Stem Cell Manufacturingmarket is expected to grow at the fastest rate during the forecast period.

Global Stem Cell ManufacturingMarketSegmentation:

By Product:

By Application:

By Technology:

By Therapy:

Global Stem Cell ManufacturingMarket Key Competitors:

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Global Stem Cell Manufacturing Market Value Projected To Reach USD 21.71 Billion By 2029, Registering A CAGR Of 9.1% - Digital Journal

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After a meeting like the 2022 ASCO Annual Meeting, one cannot help but be reinvigorated to continue advancing cancer care and feel optimistic about the future of oncology, says John M. Burke, MD.

After seeing all the amazing presentations at the American Society of Oncology (ASCO) Annual Meeting, I cannot help but reflect on how far our field has come over the course of my 20-year career.

In 2000, I moved from San Francisco, California, to New York, New York, to begin my fellowship at Memorial Sloan Kettering Cancer Center. My first rotation was on the inpatient myeloma, lymphoma, and autologous stem cell transplant service, where I encountered patients with myeloma and painful bone lesions causing fractures and spinal cord compressions. We treated patients with myeloma with chemotherapy and autologous stem cell transplant. Thalidomide (Thalomid) was starting to make a splash by showing strong efficacy in myeloma trials, and bortezomib (Velcade) emerged during those years, as well.

Nevertheless, the state of the art was exemplified by an article in the New England Journal of Medicine in 2003, describing the results of an Intergroupe Francophone du Mylome (IFM) trial. Myeloma patients were treated with vincristine, doxorubicin, and dexamethasone induction followed by single or double autologous stem cell transplant. The median event-free survival was 2 years and the median overall survival was 4 years, which seem grim by modern standards.

Fast forward about 20 years to the Plenary Session of the 2022 ASCO Annual Meeting, at which we saw the results of modern therapy in the DETERMINATION trial (NCT01208662). Patients treated with the modern standard regimen of lenalidomide (Revlimid), bortezomib, and dexamethasone followed by autologous stem cell transplant achieved a median progression-free survival of 5.5 years. In the IFM trial 20 years ago, approximately 50% of patients were alive at 4 years. In DETERMINATION, 85% of patients were alive at 4 years. Weve come a long way.

DETERMINATION represents only an infinitesimal fraction of the degree of innovation demonstrated at the ASCO meeting: an antibody-drug conjugate besting conventional chemotherapy in patients with low expression of the HER2 target in breast cancer; a KRAS inhibitor demonstrating marked activity in KRAS-mutated nonsmall cell lung cancer; a bispecific antibody redirecting T cells to suppress diffuse large B-cell lymphoma; an antibody-drug conjugate added to chemotherapy, extending survival in Hodgkin lymphoma compared with the decades-old standard-of-care regimen; and a checkpoint inhibitor rendering mismatch repairdeficient rectal cancer completely helpless.

After a meeting like this, one cannot help but be reinvigorated to continue advancing cancer care and feel optimistic about the future of oncology. We have a lot of progress to celebrateand a lot more to accomplish.

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Innovative Therapies, Care Equity Highlight 2022 ASCO Annual Meeting - Targeted Oncology

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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.

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

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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

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Repair of Traumatic Brain Injury | SCCAA - Dove Medical Press

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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).

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

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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

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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

In this free webinar, learn how live cell metabolic analysis paves the way not only for metabolic research, but also the manufacturing of significant cell and gene therapy (CGT) products. Attendees will learn how glycolysis metabolic process can be measured directly through the continuous measuring of glucose and lactate amounts in the culture media using electrochemical sensors which provides new scientific insights. The featured speakers will discuss how continuous monitoring is effectively utilized for the process development stage of CGT products and quality control during the manufacturing stage of CGT products. The speakers will also discuss how glucose and lactate can be monitored in the traditional lab environment using conventional 24-well plate and CO2 incubators without any sampling.

TORONTO (PRWEB) July 12, 2022

Among the various biological functions cells carry out to maintain life, metabolism is the key activity used to process nutrient molecules. It is also closely associated with cell proliferation and differentiation. Cell metabolic analysis would be very helpful to monitor these activities.

In the field of cancer immunotherapy such as CAR T and TCR-T therapy, stem cell research including embryonic stem (ES) and induced pluripotent stem (iPS) cells and commercial cell and gene therapy (CGT) manufacturing process development investigating and understanding the metabolic activities of cells are critical. To meet this need in the field, PHC Corporation will launch a continuous metabolic analyzer which leads to real-time visualization of the metabolic condition of living cells. This development will encourage new discoveries that have not been seen in previous studies.

Register for this webinar to learn how live cell metabolic analysis paves the way not only for metabolic research, but also the manufacturing of significant CGT products.

Join experts from PHC Corporation of North America, Ryosuke Takahashi, PhD VP, Cell and Gene Therapy Business; and Kenan Moss, Application Specialist, for the live webinar on Tuesday, July 26, 2022, at 11am EDT (4pm BST).

For more information, or to register for this event, visit Live Cell Metabolic Analysis Paving the Way for Metabolic Research and Cell & Gene Therapy.

ABOUT XTALKS

Xtalks, powered by Honeycomb Worldwide Inc., is a leading provider of educational webinars to the global life science, food and medical device community. Every year, thousands of industry practitioners (from life science, food and medical device companies, private & academic research institutions, healthcare centers, etc.) turn to Xtalks for access to quality content. Xtalks helps Life Science professionals stay current with industry developments, trends and regulations. Xtalks webinars also provide perspectives on key issues from top industry thought leaders and service providers.

To learn more about Xtalks visit http://xtalks.comFor information about hosting a webinar visit http://xtalks.com/why-host-a-webinar/

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Live Cell Metabolic Analysis Paving the Way for Metabolic Research and Cell & Gene Therapy, Upcoming Webinar Hosted by Xtalks - Benzinga

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By Nathan Sager

Published July 14, 2022 at 5:16 pm

A renowned burns specialist and his entire lab are continuing their work to develop 3-D printed skin at McMaster University in Hamilton.

Earlier this month, Dr. Marc Jeschke began a dual role at McMaster and Hamilton Health Sciences (HHS). Jeschke, who previously worked at the University of Toronto and Sunnybrook hospital, is now a professor of surgery at Mac and vice-president, research at HHS as well as medical director of its burns unit.

As part of the move, Jeschke is bringing his nearly 20-scientist burn research lab to Hamilton. The lab is supported by a gift from Charles and Margaret Juravinski through the Juravinski Research Institute. In a release from the university, Jeschke said McMaster is uniquely positioned for work across verious medical disciplines, since there are many partnerships with HHS and St. Josephs Healthcare Hmailton.

(McMaster) offers a more intimate environment than other institutions of its calibre and the quality of collaboration here is outstanding, said Jeschke.

People who suffer extensive and serious burns often end up with scarring for life. The Jeschke-headed lab has been developing a skin derivative that uses a patients own stem cells. It might one day greatly reduce scarring for people with extensive burns.

In 2020, researchers and developers from U of T and Sunnybrook became the first Canadian team to be honoured with a top prize from the 3D Pioneers Challenge for building and refining of the ReverTome handheld 3D skin printer. The printer can make new skin grown from stem cells in order to improve healing. Jeschke and his team contributed stem cell research to help inform development of the device.

The 3D Pioneers Challenge honours innovations in digital printing. The U of T-Sunnybrook team won from among a field of 52 finalists from 28 nations.

Jeschke said in the release that the therapy his lab is testing proved effective in porcine models. The clinical trial stage would be next.

The human body is so complex, but this stem-cell based therapy, if successful, will certainly change the way we care for burns and other injuries, he said.

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McMaster in Hamilton founds burn injury research program that is working on 3-D skin | inTheHammer - insauga.com

Skin Stem Cells Comments Off on McMaster in Hamilton founds burn injury research program that is working on 3-D skin | inTheHammer – insauga.com | July 16th, 2022

In molecular biologist David Sinclair's lab at Harvard Medical School, old mice are growing young again.

Using proteins that can turn an adult cell into a stem cell, Sinclair and his team have reset aging cells in mice to earlier versions of themselves. In his team's first breakthrough, published in late 2020, old mice with poor eyesight and damaged retinas could suddenly see again, with vision that at times rivaled their offspring's.

"It's a permanent reset, as far as we can tell, and we think it may be a universal process that could be applied across the body to reset our age," said Sinclair, who has spent the last 20 years studying ways to reverse the ravages of time.

"If we reverse aging, these diseases should not happen. We have the technology today to be able to go into your hundreds without worrying about getting cancer in your 70s, heart disease in your 80s and Alzheimer's in your 90s." Sinclair told an audience at Life Itself, a health and wellness event presented in partnership with CNN.

"This is the world that is coming. It's literally a question of when and for most of us, it's going to happen in our lifetimes," Sinclair told the audience.

"His research shows you can change aging to make lives younger for longer. Now he wants to change the world and make aging a disease," said Whitney Casey, an investor who is partnering with Sinclair to create a do-it-yourself biological age test.

While modern medicine addresses sickness, it doesn't address the underlying cause, "which for most diseases, is aging itself," Sinclair said. "We know that when we reverse the age of an organ like the brain in a mouse, the diseases of aging then go away. Memory comes back; there is no more dementia.

"I believe that in the future, delaying and reversing aging will be the best way to treat the diseases that plague most of us."

A reset button

In Sinclair's lab, two mice sit side by side. One is the picture of youth, the other gray and feeble. Yet they are brother and sister, born from the same litter -- only one has been genetically altered to age faster.

If that could be done, Sinclair asked his team, could the reverse be accomplished as well? Japanese biomedical researcher Dr. Shinya Yamanaka had already reprogrammed human adult skin cells to behave like embryonic or pluripotent stem cells, capable of developing into any cell in the body. The 2007 discovery won the scientist a Nobel Prize, and his "induced pluripotent stem cells," soon became known as "Yamanaka factors."

However, adult cells fully switched back to stem cells via Yamanaka factors lose their identity. They forget they are blood, heart and skin cells, making them perfect for rebirth as "cell du jour," but lousy at rejuvenation. You don't want Brad Pitt in "The Curious Case of Benjamin Button" to become a baby all at once; you want him to age backward while still remembering who he is.

Labs around the world jumped on the problem. A study published in 2016 by researchers at the Salk Institute for Biological Studies in La Jolla, California, showed signs of aging could be expunged in genetically aged mice, exposed for a short time to four main Yamanaka factors, without erasing the cells' identity.

But there was a downside in all this research: In certain situations, the altered mice developed cancerous tumors.

Looking for a safer alternative, Sinclair lab geneticist Yuancheng Lu chose three of the four factors and genetically added them to a harmless virus. The virus was designed to deliver the rejuvenating Yamanaka factors to damaged retinal ganglion cells at the back of an aged mouse's eye. After injecting the virus into the eye, the pluripotent genes were then switched on by feeding the mouse an antibiotic.

"The antibiotic is just a tool. It could be any chemical really, just a way to be sure the three genes are switched on," Sinclair said. "Normally they are only on in very young developing embryos and then turn off as we age."

Amazingly, damaged neurons in the eyes of mice injected with the three cells rejuvenated, even growing new axons, or projections from the eye into the brain. Since that original study, Sinclair said his lab has reversed aging in the muscles and brains of mice and is now working on rejuvenating a mouse's entire body.

"Somehow the cells know the body can reset itself, and they still know which genes should be on when they were young," Sinclair said. "We think we're tapping into an ancient regeneration system that some animals use -- when you cut the limb off a salamander, it regrows the limb. The tail of a fish will grow back; a finger of a mouse will grow back."

That discovery indicates there is a "backup copy" of youthfulness information stored in the body, he added.

"I call it the information theory of aging," he said. "It's a loss of information that drives aging cells to forget how to function, to forget what type of cell they are. And now we can tap into a reset switch that restores the cell's ability to read the genome correctly again, as if it was young."

While the changes have lasted for months in mice, renewed cells don't freeze in time and never age (like, say, vampires or superheroes), Sinclair said. "It's as permanent as aging is. It's a reset, and then we see the mice age out again, so then we just repeat the process.

"We believe we have found the master control switch, a way to rewind the clock," he added. "The body will then wake up, remember how to behave, remember how to regenerate and will be young again, even if you're already old and have an illness."

Science already knows how to slow human aging

Studies on whether the genetic intervention that revitalized mice will do the same for people are in early stages, Sinclair said. It will be years before human trials are finished, analyzed and, if safe and successful, scaled to the mass needed for a federal stamp of approval.

While we wait for science to determine if we too can reset our genes, there are many other ways to slow the aging process and reset our biological clocks, Sinclair said.

"The top tips are simply: Focus on plants for food, eat less often, get sufficient sleep, lose your breath for 10 minutes three times a week by exercising to maintain your muscle mass, don't sweat the small stuff and have a good social group," Sinclair said.

What controls the epigenome? Human behavior and one's environment play a key role. Let's say you were born with a genetic predisposition for heart disease and diabetes. But because you exercised, ate a plant-focused diet, slept well and managed your stress during most of your life, it's possible those genes would never be activated. That, experts say, is how we can take some of our genetic fate into our own hands.

Cutting back on food -- without inducing malnutrition -- has been a scientifically known way to lengthen life for nearly a century. Studies on worms, crabs, snails, fruit flies and rodents have found restricting calories "delay the onset of age-related disorders" such as cancer, heart disease and diabetes, according to the National Institute on Aging. Some studies have also found extensions in life span: In a 1986 study, mice fed only a third of a typical day's calories lived to 53 months -- a mouse kept as a pet may live to about 24 months.

Studies in people, however, have been less enlightening, partly because many have focused on weight loss instead of longevity. For Sinclair, however, cutting back on meals was a significant factor in resetting his personal clock: Recent tests show he has a biological age of 42 in a body born 53 years ago.

"I've been doing a biological test for 10 years now, and I've been getting steadily younger for the last decade," Sinclair said. "The biggest change in my biological clock occurred when I ate less often -- I only eat one meal a day now. That made the biggest difference to my biochemistry."

Additional ways to turn back the clock

Sinclair incorporates other tools into his life, based on research from his lab and others. In his book "Lifespan: Why We Age and Why We Don't Have To," he writes that little of what he does has undergone the sort of "rigorous long-term clinical testing" needed to have a "complete understanding of the wide range of potential outcomes." In fact, he added, "I have no idea if this is even the right thing for me to be doing."

With that caveat, Sinclair is willing to share his tips: He keeps his starches and sugars to a minimum and gave up desserts at age 40 (although he does admit to stealing a taste on occasion). He eats a good amount of plants, avoids eating other mammals and keeps his body weight at the low end of optimal.

He exercises by taking a lot of steps each day, walks upstairs instead of taking an elevator and visits the gym with his son to lift weights and jog before taking a sauna and a dip in an ice-cold pool. "I've got my 20-year-old body back," he said with a smile.

Speaking of cold, science has long thought lower temperatures increased longevity in many species, but whether it is true or not may come down to one's genome, according to a 2018 study. Regardless, it appears cold can increase brown fat in humans, which is the type of fat bears use to stay warm during hibernation. Brown fat has been shown to improve metabolism and combat obesity.

Sinclair takes vitamins D and K2 and baby aspirin daily, along with supplements that have shown promise in extending longevity in yeast, mice and human cells in test tubes.

One supplement he takes after discovering its benefits is 1 gram of resveratrol, the antioxidant-like substance found in the skin of grapes, blueberries, raspberries, mulberries and peanuts.

He also takes 1 gram of metformin, a staple in the arsenal of drugs used to lower blood sugars in people with diabetes. He added it after studies showed it might reduce inflammation, oxidative damage and cellular senescence, in which cells are damaged but refuse to die, remaining in the body as a type of malfunctioning "zombie cell."

However, some scientists quibble about the use of metformin, pointing to rare cases of lactic acid buildup and a lack of knowledge on how it functions in the body.

Sinclair also takes 1 gram of NMN, or nicotinamide mononucleotide, which in the body turns into NAD+, or nicotinamide adenine dinucleotide. A coenzyme that exists in all living cells, NAD+ plays a central role in the body's biological processes, such as regulating cellular energy, increasing insulin sensitivity and reversing mitochondrial dysfunction.

When the body ages, NAD+ levels significantly decrease, dropping by middle age to about half the levels of youth, contributing to age-related metabolic diseases and neurodegenerative disorders. Numerous studies have shown restoring NAD+ levels safely improves overall health and increases life span in yeast, mice and dogs. Clinical trials testing the molecule in humans have been underway for three years, Sinclair said.

"These supplements, and the lifestyle that I am doing, is designed to turn on our defenses against aging," he said. "Now, if you do that, you don't necessarily turn back the clock. These are just things that slow down epigenetic damage and these other horrible hallmarks of aging.

"But the real advance, in my view, was the ability to just tell the body, 'Forget all that. Just be young again,' by just flipping a switch. Now I'm not saying that we're going to all be 20 years old again," Sinclair said.

"But I'm optimistic that we can duplicate this very fundamental process that exists in everything from a bat to a sheep to a whale to a human. We've done it in a mouse. There's no reason I can think of why it shouldn't work in a person, too."

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The 'Benjamin Button' effect: Scientists can reverse aging in mice. The goal is to do the same for humans - KITV Honolulu

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ICYMI: Amazon Prime Day is coming to an end tonight and truth be told, the sales appear to be gifts that keep on giving. One of our favorite skin-care tools is having a major discount across all of its devices and treatments. Yep, you guessed it, it's NuFace.

If you're unfamiliar with the brand and the magic it can do, let us school you quickly. NuFace devices use microcurrent technology that the brand calls "fitness for your face." In the same way that consistently hitting weights and cardio whips our body's muscles into shape, the metal nodes on the head of the tools send electrical currents through the various layers of facial skin, down to the muscles, to basically give them a workout.

Into it? Well, lucky for you NuFace products will be available at a discount throughout this two-day epic sale. Starting right now through July 13, you can snag devices, boosters, and activators for up to 36 percent off. The sale includes top-selling products like the Trinity, NuBody, Fix, and more.

So what are you waiting for? This luxury tool rarely goes on sale so get to shopping because these discounts end later on when Prime Day closes its virtual doors.

NuFace Trinity Starter Kit

NuFace Trinity Complete Kit

Both the Trinity Starter Kit and Complete Kit are essentially the same thing, but the complete kit comes with some additional attachments. Both kits feature a NuFace device and a gel primer to apply prior in order to activate the current. However, the Complete Kit holds a dual wand that targets specific areas like around the lips and eyes and a LED light attachment that helps reduce the appearance of fine lines and wrinkles.

If you're not into breaking the $200 mark, consider the Mini Starter Kit it holds the same device and gel primer, just in a smaller (more portable!) version that achieves the same results.

The NuBody features those same nodes on the head as the Trinity but in a handheld body version that utilizes four nodes. With four electrical currents, this device sends waves through the skin down to the muscles to help sculpt and tone the body. Plus, you get a 10-ounce gel primer to ensure the device glides smoothly and evenly.

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NuFace Is Having a Major Sale During Amazon Prime Day 2022 See Deals on Trinity, NuBody, and More - Allure

Skin Stem Cells Comments Off on NuFace Is Having a Major Sale During Amazon Prime Day 2022 See Deals on Trinity, NuBody, and More – Allure | July 16th, 2022

Endometriosis is a condition that can occur when tissue that is normally found lining the uterus, known as the endometrium, begins to grow outside of that organ. With this disorder, the tissue can be found growing around other nearby organs the ovaries, intestines, and even tissue that lines your pelvis.

Because endometrial tissue is affected by hormonal changes during the menstrual cycle, its not uncommon for people with endometriosis to experience pain and discomfort just like they would with endometrial tissue in the uterus. And just like that tissue, this tissue breaks down too but isnt expelled.

As a result, endometriosis can lead to the growth of scar tissue, irritation, and even infertility. But while much is known about endometriosis in adult women, the condition isnt as well-researched in children or adolescents.

Officially, there is no known cause of endometriosis regardless of the age at which its discovered. And almost all researchers agree that limited studies in younger age groups, as well as healthcare professionals delaying diagnosis by several years, can contribute to its progression that often leads to infertility and other negative outcomes.

There are a few theories that highlight potential reasons, but no theory has proven to be conclusive yet. Well take a closer look at the best supported theories to-date:

Retrograde menstruation is a condition in which blood that is expelled from the uterus flows back toward the fallopian tubes rather than out of the body through the vagina. This scenario is more common than you may expect, with roughly 90% of women experiencing it at some point during their menstruating lives.

But for some, this backflow can lead to endometrial cells adhering to organs or cavity tissues, or whats known as endometrial lesions. This is why it is currently considered a key factor in developing endometriosis.

A 2013 study conducted in Japan found a link between the incidence of menstrual pain and the need for medical interventions. While the study found that roughly a third of all menstruating Japanese women experienced pain significant enough to require medication, of that group, 6% did not experience any improvement after taking medication.

More importantly, this study found that roughly 25 to 38% of adolescents that complained of chronic pelvic pain were later diagnosed with endometriosis. Meanwhile, the most common solution offered to adolescents is pain medications, which will not treat the cause of the pain.

That same 2013 Japanese study noted that some respondents were diagnosed with endometriosis while having never menstruated (premenarchal). This discovery has encouraged researchers to consider that other underlying mechanisms might contribute to endometriosis rather than retrograde menstruation.

Some researchers further hypothesized that endometriosis diagnoses in premenarchal participants could be caused by stem cells that later develop into endometrial tissue and are later activated when menstruation begins.

While we often think of endometriosis as a condition exclusively impacting women, the reality is that it can also develop in nonbinary or transmasculine (people assigned female at birth that later transition to boys) adolescents as well.

A 2020 study reviewed previous research that focused on 35 trans participants ages 26 and younger that were diagnosed with dysmenorrhea (or menstruation-related pain) and treated for that condition. Of the 35, seven of the patients were evaluated and found to have endometriosis some of which were diagnosed after transitioning and included one participant that had already begun testosterone treatment.

Of the seven patients, treatment varied from oral contraceptives, testosterone treatment, and other drugs such as danazol and progestins. The study found that results were mixed. While some respondents found success with testosterone therapy for resolving symptoms, this wasnt the case for everyone.

Ultimately, the study recommended that trans masculine people experiencing dysmenorrhea symptoms should be screened for endometriosis, and that testosterone therapy alone isnt necessarily a complete solution.

Although less is known about endometriosis in adolescent or teenage populations, symptoms tend to be consistent with those found in adult women. These include:

If you or your child is experiencing symptoms of endometriosis, keep reading to learn about getting diagnosed.

Consistently, the research and medical communities agree that early detection of endometriosis is the best way to prevent acute spread which can lead to infertility. Checking for endometriosis on your own is not possible. But letting your doctor know that youre experiencing chronic pelvic pain, heavy or long periods, or any of the other common symptoms associated with endometriosis is important.

Your physician might start the diagnostic process by performing a pelvic ultrasound to ensure that any other underlying conditions or infections arent causing your symptoms. Usually, endometriosis is diagnosed with laparoscopy. This is a minimally invasive procedure where your physician inserts a thin tube with a light and lens through a small incision into the lower abdomen. With this procedure, they can look for endometrial lesions to determine if endometriosis is present.

Unfortunately, its common for period pain to be dismissed as a regular part of life, and for many people it can take more than a decade to receive a proper diagnosis. If this is the case for you, dont hesitate to advocate for yourself and seek a second opinion if youre unable to find a treatment plan that works for you.

Currently, there is no cure for endometriosis. However, just as in adults, the goal of treating adolescent endometriosis is to control and prevent disease progression, provide symptom relief, and preserve fertility.

Several treatment methods may be recommended depending on the amount of endometrial tissue that is present (disease progression).

Treatment options can center on hormonal therapy to control estrogen levels a key factor that influences endometrial growth. For some patients, this might include taking oral contraception, or a progestin-only agent to prevent or minimize the onset of periods, as well as nonsteroidal anti-inflammatory drugs (NSAIDs) for pain management.

Be aware that you might need to try several different types of hormonal therapies before you find the right option that controls your condition.

Some patients might also be prescribed Gonadotropin-releasing hormone (GnRH) agonist therapy. But this is usually reserved for adults, because research suggests that this treatment can impact bone mineralization in adolescents.

Surgery is often used for both diagnosis and treatment. While some surgeries can remove endometrial lesions, this is not a permanent solution for everyone.

Research has proven that even with surgery, endometrial lesions can return.

Most endometriosis conversations center around female patients. But its important to remember that trans men as well as those born male are also at risk of developing this disease.

Once thought to only be an issue for menstruating females, research suggests that endometriosis can also be detected in premenarchal youth.

Theres no cure for endometriosis. But experts, advocates, and the medical community agree that early interventions for the condition are critical for limiting its spread, controlling symptoms that can impact everyday life, and preserving fertility especially in adolescents.

Excerpt from:
Endometriosis in Teens: Causes, Symptoms, and Treatment - Healthline

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Bone Therapeutics optimizes statistical analysis and introduces interim analysis in the ongoing ALLOB Phase IIb study for high-risk tibial fractures

Global News Feed Comments Off on Bone Therapeutics optimizes statistical analysis and introduces interim analysis in the ongoing ALLOB Phase IIb study for high-risk tibial fractures | July 16th, 2022

Novozymes has experienced unprecedented cost-inflation on raw materials, energy, and logistics. To recover these headwinds, substantial price increases will be implemented.

Originally posted here:
Novozymes plan to further increase prices across the portfolio in response to the significant and persistent hike in incoming cost

Global News Feed Comments Off on Novozymes plan to further increase prices across the portfolio in response to the significant and persistent hike in incoming cost | July 16th, 2022