Cell Separation Technologies Market Expands with Rise in Prevalence of Chronic Diseases, States TMR Study – GlobeNewswire
By daniellenierenberg
Wilmington, Delaware, United States, July 18, 2022 (GLOBE NEWSWIRE) -- Transparency Market Research Inc.: The market value of the global cell separation technologies market is estimated to be over US$ 20.3 Bn by 2031, according to a research report by Transparency Market Research (TMR). Hence, the market is expected expand at a CAGR of 11.9% during the forecast period, from 2022 to 2031.
According to the TMR insights on the cell separation technologies market, the prevalence of chronic disorders including obesity, diabetes, cardiac diseases, cancer, and arthritis is being increasing around the world. Some of the key reasons for this situation include the sedentary lifestyle of people, increase in the older population, and rise in cigarette smoking and alcohol consumption across many developed and developing nations. These factors are expected to help in the expansion of the cell separation technologies market during the forecast period.
Players in the global cell separation technologies market are increasing focus on the launch of next-gen products. Hence, they are seen increasing investments in R&Ds. Moreover, companies are focusing on different strategies including acquisitions and strengthening their distribution networks in order to stay ahead of the competition.
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As per the Imperial College London, chronic diseases are expected to account for approximately 41 million deaths per year, which seven out of 10 demises worldwide. Of these deaths, approximately 17 million are considered to be premature. Hence, surge in cases of chronic diseases globally is resulting into increased need for cellular therapies in order to treat such disease conditions, which, in turn, is boosting the investments toward R&Ds, creating sales opportunities in the cell separation technologies market.
Cell Separation Technologies Market: Key Findings
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Cell Separation Technologies Market: Growth Boosters
Cell Separation Technologies Market: Regional Analysis
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Cell Separation Technologies Market: Key Players
Some of the key players profiled in the report are:
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Cell Separation Technologies Market Segmentation
Modernization of healthcare in terms of both infrastructure and services have pushed the healthcare industry to new heights, Stay Updated with Latest Healthcare Research Reports by Transparency Market Research:
Cell Culture Market: Rise in outsourcing activities and expansion of biopharmaceutical manufacturers are expected to drive the cell culture market during the forecast period
Cell Culture Media, Sera, and Reagents Market: The global cell culture media, sera, and reagents market is majorly driven by growth and expansion of biotechnology & pharmaceutical companies and academic & research institutes.
Stem Cells Market: The global stem cells market is majorly driven by rising applications of stem cells in regenerative medicines. Increase in the number of chronic diseases such as cardiac diseases, diabetes, cancer, etc.
Cell Line Authentication and Characterization Tests Market: Increase in the geriatric population and surge in incidence of chronic diseases are projected to drive the global cell line authentication and characterization tests market.
CAR T-cell Therapy Market: The CAR T-cell therapy market is expected to clock a CAGR of 30.6% during the assessment period. The CAR T-cell therapy is known as a revolutionary treatment option for cancer, owing to its remarkably effective and durable clinical responses.
Cell & Tissue Preservation Market: Rise in investments in the field of regenerative medicine research is estimated to propel the market. Human blood, tissues, cells, and organs own the capability to heal damaged tissues and organs with long-term advantages.
Placental Stem Cell Therapy Market: Placental stem cell therapy market is driven by prominence in treatment of age-related disorders/diseases and increase in awareness about stem cell therapies are projected to drive the global market in the near future.
Biotherapeutics Cell Line Development Market: The market growth will be largely driven by research and development activities due to which, new solutions and technologies have gradually entered the market.
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Transparency Market Research, a global market research company registered at Wilmington, Delaware, United States, provides custom research and consulting services. Our exclusive blend of quantitative forecasting and trends analysis provides forward-looking insights for thousands of decision makers. Our experienced team of Analysts, Researchers, and Consultants use proprietary data sources and various tools & techniques to gather and analyze information.
Our data repository is continuously updated and revised by a team of research experts, so that it always reflects the latest trends and information. With a broad research and analysis capability, Transparency Market Research employs rigorous primary and secondary research techniques in developing distinctive data sets and research material for business reports.
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Cell Separation Technologies Market Expands with Rise in Prevalence of Chronic Diseases, States TMR Study - GlobeNewswire
Dental Membrane and Bone Graft Substitutes Market to Exceed Value of US$ 1,337 Mn by 2031 – PR Newswire UK
By daniellenierenberg
WILMINGTON, Del., July 21, 2022 /PRNewswire/ --An in-depth demand analysis of dental membrane and bone graft substitutes found that massive demand for resorbable bone grafting materials presents value-grab opportunity. Companies in the dental membrane and bone graft substitutes market are actively leaning on development of novel biomaterials to meet the needs of bone grafting procedures. The TMR study projects the size of the market to surpass worth of US$ 1,337 Mn by 2031.
Advancements in periodontology are catalyzing introduction of new soft tissue regeneration, as emerging trends of the dental membrane and bone graft substitutes market underscore. Moreover, dental membrane and bone graft substitutes market projections in the TMR study have found that the use of xenograft for dental bone regeneration is anticipated to rise rapidly, and will unlock lucrative avenues. The fact that xenografts are cost-effective and show good results in bone tissue regeneration will spur the popularity of products in the segment.
Increasing number of bone regeneration procedures has led to the commercialization of novel biomaterials and dental bone grafts. The application of human cell sources in bone graft substitutes is growing, thus extending the canvas for companies in the dental membrane and bone graft substitutes market. Rise in oral disorders and injuries has impelled the need for bone substitute materials that can promise long-term survival rates in the patients.
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Key Findings of Dental Membrane and Bone Graft Substitutes Market Study
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Dental Membrane and Bone Graft Substitutes Market: Key Drivers
Dental Membrane and Bone Graft Substitutes Market: Regional Growth Dynamics
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Dental Membrane and Bone Graft Substitutes Market: Key Players
High degree of fragmentation has characterized the competition landscape in the dental membrane and bone graft substitutes market, mainly due to presence of several prominent players. Some of the key players are Zimmer Biomet, OPKO Health, Inc., NovaBone Products, LLC., Nobel Biocare Services AG, Geistlich Pharma AG, Dentsply Sirona, Collagen Matrix, Inc., BioHorizons, and Institut Straumann AG.
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Dental Membrane and Bone Graft Substitutes Market Segmentation
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Modernization of healthcare in terms of both infrastructure and services have pushed the healthcare industry to new heights, Stay Updated withLatest Healthcare Research Reportsby Transparency Market Research:
Non-Invasive Prenatal Testing Market: Non-invasive prenatal testing market was worth around US$ 1.3 Bn in 2018. The market is likely to develop at a CAGR of 16.4% during the forecast period, from 2019 to 2027.
Cell Culture Media, Sera, and Reagents Market: The global cell culture media, sera, and reagents market is majorly driven by growth and expansion of biotechnology & pharmaceutical companies and academic & research institutes.
Stem Cells Market: The global stem cells market is majorly driven by rising applications of stem cells in regenerative medicines. Increase in the number of chronic diseases such as cardiac diseases, diabetes, cancer, etc.
Cell Line Authentication and Characterization Tests Market: Increase in the geriatric population and surge in incidence of chronic diseases are projected to drive the global cell line authentication and characterization tests market.
CAR T-cell Therapy Market: The CAR T-cell therapy market is expected to clock a CAGR of 30.6% during the assessment period. The CAR T-cell therapy is known as a revolutionary treatment option for cancer, owing to its remarkably effective and durable clinical responses.
Cell & Tissue Preservation Market: Rise in investments in the field of regenerative medicine research is estimated to propel the market. Human blood, tissues, cells, and organs own the capability to heal damaged tissues and organs with long-term advantages.
mHealth Monitoring Diagnostic Medical Devices Market: The global mHealth monitoring diagnostic medical devices market was valued at US$ 29.05 Bn in 2018 and is projected to expand at a CAGR of 20.5% from 2019 to 2027.
Pediatric Medical Devices Market: The global pediatric medical devices market was valued at US$ 21,000 Mn in 2017 and is projected to expand at a CAGR of 8.0% from 2018 to 2026.
About Transparency Market Research
Transparency Market Research, a global market research company registered at Wilmington, Delaware, United States, provides custom research and consulting services. Our exclusive blend of quantitative forecasting and trends analysis provides forward-looking insights for thousands of decision makers. Our experienced team of Analysts, Researchers, and Consultants use proprietary data sources and various tools & techniques to gather and analyze information.
Our data repository is continuously updated and revised by a team of research experts, so that it always reflects the latest trends and information. With a broad research and analysis capability, Transparency Market Research employs rigorous primary and secondary research techniques in developing distinctive data sets and research material for business reports.
For More Research Insights on Leading Industries, Visit Our YouTube Channel and hit subscribe for Future Update -https://www.youtube.com/channel/UC8e-z-g23-TdDMuODiL8BKQ
Contact :Rohit BhiseyTransparency Market Research Inc.CORPORATE HEADQUARTER DOWNTOWN,1000 N. West Street,Suite 1200, Wilmington, Delaware 19801 USATel: +1-518-618-1030USA Canada Toll Free: 866-552-3453Website:https://www.transparencymarketresearch.comBlog:https://tmrblog.comEmail:sales@transparencymarketresearch.com
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Dental Membrane and Bone Graft Substitutes Market to Exceed Value of US$ 1,337 Mn by 2031 - PR Newswire UK
Innovative Therapies, Care Equity Highlight 2022 ASCO Annual Meeting – Targeted Oncology
By daniellenierenberg
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
Global Stem Cell Manufacturing Market Value Projected To Reach USD 21.71 Billion By 2029, Registering A CAGR Of 9.1% – Digital Journal
By daniellenierenberg
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.
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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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SNUH team finds a key cell that keeps top hematopoietic stem cells young – KBR
By daniellenierenberg
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
Repair of Traumatic Brain Injury | SCCAA – Dove Medical Press
By daniellenierenberg
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.
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By daniellenierenberg
Fibrosis is the thickening of various tissues caused by the deposition of fibrillar extracellular matrix (ECM) in tissues and organs as part of the bodys wound healing response to various forms of damage. When accompanied by chronic inflammation, fibrosis can go into overdrive and produce excess scar tissue that can no longer be degraded. This process causes many diseases in multiple organs, including lung fibrosis induced by smoking or asbestos, liver fibrosis induced by alcohol abuse, and heart fibrosis often following heart attacks. Fibrosis can also occur in the bone marrow, the spongy tissue inside some bones that houses blood-producing hematopoietic stem cells (HSCs) and can lead to scarring and the disruption of normal functions.
Chronic blood cancers known as myeloproliferative neoplasms (MPNs) are one example, in which patients can develop fibrotic bone marrow, or myelofibrosis, that disrupts the normal production of blood cells. Monocytes, a type of white blood cell belonging to the group of myeloid cells, are overproduced from HSCs in neoplasms and contribute to the inflammation in the bone marrow environment, or niche. However, how the fibrotic bone marrow niche itself impacts the function of monocytes and inflammation in the bone marrow was unknown.
Now, a collaborative team from Penn, Harvard, the Dana-Farber Cancer Institute (DFCI), and Brigham and Womens Hospital has created a programmable hydrogel-based in vitro model mimicking healthy and fibrotic human bone marrow. Combining this system with mouse in vivo models of myelofibrosis, the researchers demonstrated that monocytes decide whether to enter a pro-inflammatory state and go on to differentiate into inflammatory dendritic cells based on specific mechanical properties of the bone marrow niche with its densely packed ECM molecules. Importantly, the team found a drug that could tone down these pathological mechanical effects on monocytes, reducing their numbers as well as the numbers of inflammatory myeloid cells in mice with myelofibrosis. The findings are published in Nature Materials.
We found that stiff and more elastic slow-relaxing artificial ECMs induced immature monocytes to differentiate into monocytes with a pro-inflammatory program strongly resembling that of monocytes in myelofibrosis patients, and the monocytes to differentiate further into inflammatory dendritic cells, says co-first author Kyle Vining, who recently joined Penn.More viscous fast-relaxing artificial ECMs suppressed this myelofibrosis-like effect on monocytes. This opened up the possibility of a mechanical checkpoint that could be disrupted in myelofibrotic bone marrow and also may be at play in other fibrotic diseases. Vining will be appointedassistant professor of preventive and restorative sciences in theSchool of Dental Medicine and the Department of Materials Sciences in theSchool of Engineering and Applied Science, pending approval by Penn Dental Medicines personnel committees and the Provosts office.
Vining worked on the study as a postdoctoral fellow at Harvard in the lab of David Mooney. Our study shows that the differentiation state of monocytes, which are key players in the immune system, is highly regulated by mechanical changes in the ECM they encounter, says Mooney, who co-led the study with DFCI researcher Kai Wucherpfennig. Specifically, the ECMs viscoelasticity has been a historically under-appreciated aspect of its mechanical properties that we find correlates strongly between our in vitro and the in vivo models and human disease. It turns out that myelofibrosis is a mechano-related disease that could be treated by interfering with the mechanical signaling in bone marrow cells.
Mooney is also the Robert P. Pinkas Family Professor of Bioengineering at Harvard and leads the Wyss Institutes Immuno-Materials Platform. Wucherpfennig is director of DFCIs Center for Cancer Immunotherapy Research, professor of neurobiology at Brigham and Harvard Medical School, and an associate member of the Broad Institute of MIT and Harvard. Mooney, together with co-senior author F. Stephen Hodi, also heads the Immuno-engineering to Improve Immunotherapy (i3) Center, which aims to create new biomaterials-based approaches to enhance immune responses against tumors. The new study follows the Centers road map. Hodi is director of the Melanoma Center and The Center for Immuno-Oncology at DFCI and professor of medicine at Harvard Medical School.
The mechanical properties of most biological materials are determined by their viscoelastic characteristics. Unlike purely elastic substances like a vibrating quartz, which store elastic energy when mechanically stressed and quickly recover to their original state once the stress is removed, slow-relaxing viscoelastic substances also have a viscous component. Like the viscosity of honey, this allows them to dissipate stress under mechanical strain by rapid stress relaxation. Viscous materials are thus fast-relaxing materials in contrast to slow-relaxing purely elastic materials.
The team developed an alginate-based hydrogel system that mimics the viscoelasticity of natural ECM and allowed them to tune the elasticity independent from other physical and biochemical properties. By tweaking the balance between elastic and viscous properties in these artificial ECMs, they could recapitulate the viscoelasticity of healthy and scarred fibrotic bone marrow, whose elasticity is increased by excess ECM fibers. Human monocytes placed into these artificial ECMs constantly push and pull at them and in turn respond to the materials mechanical characteristics.
Next, the team investigated how the mechanical characteristics of stiff and elastic hydrogels compared to those in actual bone marrow affected by myelofibrosis. They took advantage of a mouse model in which an activating mutation in a gene known as Jak2 causes MPN, pro-inflammatory signaling in the bone marrow, and development of myelofibrosis, similar to the disease process in human patients with MPN. When they investigated the mechanical properties of bone marrow in the animals femur bones, using a nanoindentation probe, the researchers measured a higher stiffness than in non-fibrotic bone marrow. Importantly, we found that the pathologic grading of myelofibrosis in the animal model was significantly correlated with changes in viscoelasticity, said co-first author Anna Marneth, who spearheaded the experiments in the mouse model as a postdoctoral fellow working with Ann Mullally, a principal investigator at Brigham and DFCI, and another senior author on the study.
An important question was whether monocytes response to the mechanical impact of the fibrotic bone marrow niche could be therapeutically targeted. The researchers focused on an isoform of the phosphoinositide 3-kinase (PI3K)-gamma protein, which is specifically expressed in monocytes and closely related immune cells. PI3K-gamma is known for regulating the assembly of a cell-stiffening filamentous cytoskeleton below the cell surface that expands in response to mechanical stress, which the team also observed in monocytes encountering a fibrotic ECM. When they added a drug that inhibits PI3K-gamma to stiff elastic artificial ECMs, it toned down their pro-inflammatory response and, when given as an oral treatment to myelofibrosis mice, significantly lowered the number of monocytes and dendritic cells in their bone marrow.
This research opens new avenues for modifying immune cell function in fibrotic diseases that are currently difficult to treat. The results are also highly relevant to human cancers with a highly fibrotic microenvironment, such as pancreatic cancer, says Wucherpfennig.
Adapted from a press release written by Benjamin Boettner of the Wyss Institute for Biologically Inspired Engineering at Harvard University.
Other authors on the study are Harvards Kwasi Adu-Berchie, Joshua M. Grolman, Christina M. Tringides, Yutong Liu, Waihay J. Wong, Olga Pozdnyakova, Mariano Severgnini, Alexander Stafford, and Georg N. Duda.
The study was funded by the National Cancer Institute of the National Institutes of Health (Grant CA214369), National Institute of Dental & Craniofacial Research of the National Institutes of Health (grants DE025292 and DE030084), Food and Drug Administration (Grant FD006589), and Harvard University Materials Research Science and Engineering Center (Grant DMR 1420570).
Link:
Deconstructing the mechanics of bone marrow disease | Penn Today - Penn Today
Krabbe disease, which mostly affects newborns causes, symptoms, and treatment – CNBCTV18
By daniellenierenberg
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
Scientists Discover Genes That Affect the Risk of Developing Pre-Leukemia – Newswise
By daniellenierenberg
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
Live Cell Metabolic Analysis Paving the Way for Metabolic Research and Cell & Gene Therapy, Upcoming Webinar Hosted by Xtalks – Benzinga
By daniellenierenberg
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
McMaster in Hamilton founds burn injury research program that is working on 3-D skin | inTheHammer – insauga.com
By daniellenierenberg
Preferred RegionHow does this work?
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
Endometriosis in Teens: Causes, Symptoms, and Treatment – Healthline
By daniellenierenberg
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
NuFace Is Having a Major Sale During Amazon Prime Day 2022 See Deals on Trinity, NuBody, and More – Allure
By daniellenierenberg
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
The ‘Benjamin Button’ effect: Scientists can reverse aging in mice. The goal is to do the same for humans – KITV Honolulu
By daniellenierenberg
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."
& 2022 Cable News Network, Inc., a WarnerMedia Company. All rights reserved.
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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
Stem Cells Used to Repair Heart Defects in Children – NBC 5 Dallas-Fort Worth
By daniellenierenberg
Almost one out of 100 babies are born with a heart defect each year in the United States. Many of these babies will need surgery within weeks of birth, followed by more surgeries throughout their lives. Now, doctors are turning to stem cells to give big hope for little hearts.
Hypoplastic left heart syndrome is a complex congenital heart disease. It is where the left ventricle does not develop, Sunjay Kaushal, MD, Ph.D., Chief of Pediatric Cardiac Surgery at Lurie Childrens Hospital in Chicago, explained.
Hypoplastic left heart syndrome
Those newborns depend solely on their right ventricles to pump blood throughout their bodies.
Kaushal emphasizes, These babies need surgical intervention in the first weeks of life.
Between 15% and 20% of those babies will not live to see their first birthday. For the little ones who do, medications and implanted devices can help, but ultimately, those children will need a heart transplant to survive.
That right ventricle becomes tired. It doesn't pump blood efficiently, Kaushal further explains.
The latest news from around North Texas.
Pediatric cardiac surgeons at Lurie Childrens Hospital are injecting stem cells directly into the heart to revitalize the worn-out right ventricle.
We're trying to see if we can actually put stem cells in there in order to remodel, rejuvenate that right ventricle in order to pump blood more efficiently for that baby, Kaushal said.
In the long run, stem cell therapy could possibly prevent those children from needing a heart transplant at all.
Kaushal added, I think that these studies could be game-changing for our babies.
They said 38 patients will be enrolled at seven clinical sites across the United States for a phase two clinical trial this year. Researchers hope that eventually, the stem cell injections will not have to be given as an injection into the heart, but as an intravenous injection like other medicine.
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Stem Cells Used to Repair Heart Defects in Children - NBC 5 Dallas-Fort Worth
Promising solution to fatal genetic-disorder complications discovered by University professor and Ph.D. candidate – Nevada Today
By daniellenierenberg
Affecting one in 5,000 male births worldwide, Duchenne Muscular Dystrophy (DMD) is a fatal genetic disorder that currently doesnt have a cure, but published research conducted at the University of Nevada, Reno School of Medicine shows promise and may lead to the eventual development of a new molecular therapeutic.
The latest, significant research finding, published in Human Molecular Genetics, February 2022, involves the small-molecule sunitinib which has been shown to mitigate DMD-related skeletal muscle disease in a number of ways.
As patients with DMD grow older, muscular dystrophy worsens, causing respiratory and cardiac muscle failure resulting in premature death. There are no effective treatments to prevent DMD-related cardiac failure, however continued research in the lab of UNR Med Professor of Pharmacology Dean Burkin is pointing to protein and molecular-based solutions, including sunitinib which is already FDA approved and used in cancer treatments.
Burkin conducted the latest research with Ph.D. student Ariany Oliveira-Santos. Based on a mouse model, they found that sunitinib improved major negative symptoms that stem from DMD, such as cardiac muscle damage, without depressing the immune system completely. Oliveira-Santos was lead author on the published results. The study was supported by a grant from the Muscular Dystrophy Association and the National Institutes of Health.
Burkins lab focuses mainly on studying two key proteins 71 integrinand laminin and understanding the role they play in muscle development and disease. The lab primarily studies two muscle-damaging diseases: DMD and Laminin-2 related congenital muscular dystrophy (LAMA2-CMD).
Were interested in the biology of the 71 integrin, that's really the central focus of [our research], Burkin said. But we also have other big interests in these muscle diseases where the integrin [protein] is normally found.
Burkin explains that through this translational research, which he also calls the lab bench to bedside approach, researchers attempt to understand the biology of a system as much as possible, and then continue through the development steps that lead to therapeutic treatments.
Patients with DMD lack dystrophin which causes progressive muscle degeneration and weakness. This means the more these muscles are used, the more damage occurs. While there are repair cells in muscles, these cells eventually tire out. Burkin and Oliveira-Santos noted that the heart, an organ being used all the time, does not have this repair system, making the damage severe in cardiac muscles as well. Currently some therapeutic approaches have been beneficial for skeletal muscles but not for the heart; therefore, its important to have a drug or treatment that can target and be beneficial to skeletal and cardiac muscle at the same time, Oliveira-Santos explained.
We looked to the electrical and mechanical function of the heart and both were improved, Oliveira-Santos said. Sunitinib helped the cardiac function [and reduced] cardiac damage, and inflammation. I don't think theres really many drugs out there that do that right now.
Oliveira-Santos remembers wanting to be a scientist as early as eight years old. She went on to earn degrees in Brazil, including a bachelors in biomedicine and a masters in the scientific fields of immunology and pharmacology as they relate to transplant rejection. While earning her masters degree, Burkin was invited to Brazil by Oliveira-Santoss supervisor to give a talk, and the two met in-person and discussed her masters project. At the time, they were studying the same molecule, but in different models, so Oliveira-Santos had read some of Burkins papers.
Oliveira-Santos had always been interested in the physiology and pathology of disease and thought it would be a great area to study for a doctoral degree. She knew Burkin was working in this field, so about five years after their in-person meeting, Oliveira-Santos reached out to Burkin. He told her about an open position in his lab for a Ph.D. student, and their project of understanding the role of an FDA-approved small molecule for the treatment of DMD cardiomyopathy. She felt this project was a good match for what she was looking for and joined the lab in January 2019.
Oliveira-Santos said the mentorship and support shes received from Burkin and the rest of the lab has been invaluable.
Dean is always available to discuss and very happy to help [the lab members] with everything we need, Oliveira-Santos said. Everyone had an important opinion about the project and that was essential for the projects success.
While working in science oftentimes can come with struggles, Oliveira-Santos expressed how much these experiences have taught her.
Being in science is a big challenge, because you have to learn how to deal with problems all the time, she said. There are more failures than success [so] it teaches you how to deal with failure. Failure is normal. You just need to try to find a way around to get a solution.
Oliveira-Santos is set to finish her Ph.D. in Cellular and Molecular Pharmacology & Physiology in the fall 2022.
When I bring a student to the lab, I say I can supply everything but enthusiasm. And that's one thing that Ariany brings in abundance, Burkin said. I'm putting my students in contact with other principal investigators that I know to try and make sure that the next level on their career is achieved. She can go anywhere right now and move forward. The world is her oyster.
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Promising solution to fatal genetic-disorder complications discovered by University professor and Ph.D. candidate - Nevada Today
Pneumonia and Heart Disease: What You Should Know – Healthline
By daniellenierenberg
Your heart and lungs share a close relationship, each relying on the other to replenish your blood with oxygen, remove wastes, and move blood and nutrients around your body.
When one of these players is underperforming or damaged, the other is quickly affected.
Pneumonia is an infection in one or both lungs. The tiny air sacs (alveoli) that move gases like oxygen in and out of your blood fill with fluid or pus.
This article will explore how pneumonia can affect how well your heart works and what can happen if you already have heart disease and then develop pneumonia.
Coronary artery disease is the most common form of heart disease in the United States. It develops when cholesterol and other substances build up in your blood vessels specifically the coronary arteries that supply blood to your heart.
Many things can lead to this buildup, including diet, lifestyle choices, and genetics.
The buildup of substances in your blood vessels is dangerous on its own since it can restrict blood flow to the heart and other body parts. But its even more serious when pieces of this buildup called plaques break off from the walls of your blood vessels.
When these pieces break off, they can travel to other areas of the body like the brain or heart, cutting off the blood supply to these organs resulting in a stroke or heart attack.
On its own, pneumonia is not a heart disease. Its a lung infection caused by bacteria or viruses.
However, heart disease complications like congestive heart failure can cause a condition similar to pneumonia.
Certain types of heart failure can lead to pulmonary edema. In this case, the heart is too weak to effectively pump blood out to the body, so the blood backs up into the heart and eventually into the lungs.
As this backed-up blood builds up in the lungs, pressure in the blood vessels of your lungs increases, and it can cause fluid buildup in the alveoli.
This results in an effect similar to pneumonia, where these air sacs fill with fluid.
Pneumonia is an infection that can cause inflammation throughout the body. This inflammation can lead to other complications, including an increased risk that bits of plaque can break free from your vessel walls and lead to heart attack or stroke.
Even without existing coronary artery disease or plaque buildup, the body-wide inflammation that pneumonia triggers can cause its own problems.
Inflammation can interfere with the normal function of all kinds of systems in your body especially the heart. This makes heart failure one of the most common complications of pneumonia.
About 30% of people hospitalized with community-acquired pneumonia develop heart failure and other cardiovascular problems, but the risk isnt always immediate. Research indicates that the greatest risk of heart complications occurs in the month after a pneumonia diagnosis, and the risk can continue for up to a decade.
It can be difficult to tell when pneumonia is affecting your heart, as pneumonia and heart disease can share symptoms including:
Additional symptoms you may experience with pneumonia that are not as common with heart disease include:
Inflammation in response to a pneumonia infection has some of the greatest impact on your heart.
Although heart damage from pneumonia can happen in anyone, it affects people with preexisting heart disease the most.
Among people who develop pneumonia with preexisting heart failure, about 1.4% who are treated in the outpatient setting find their heart failure gets worse after pneumonia. That percentage increases to 24% in people with more severe pneumonia that requires hospitalization.
Aside from inflammation, some individual cardiac symptoms or complications that can develop after a bout with pneumonia include:
The relationship between pneumonia and cardiovascular disease goes both ways: Pneumonia can increase the risk of heart disease, and a history of heart disease can increase the risk of pneumonia.
One 2018 study found that people with cardiovascular diseases heart failure in particular are three times more likely than others to develop community-acquired pneumonia.
Generally, the best way to prevent problems like pneumonia and heart failure is to take care of your overall health.
This means:
People with heart disease are generally recommended to stay up-to-date on various vaccinations, too. This can prevent acute infection and its complications.
However, there may be little difference in mortality rates among people with heart failure and pneumonia who had been vaccinated against things like influenza and pneumonia.
With every heartbeat and every breath, your lungs and heart work in tandem. Infections and chronic diseases that affect one organ can affect the other.
Pneumonia can increase your risk of developing heart disease or having your existing heart disease worsen. Likewise, heart disease can increase your risk of developing several types of pneumonia.
Talk with your doctor about your overall health and how to avoid chronic heart disease and acute infections like pneumonia.
Vaccines are one part of the equation, but the best strategy involves other health and diet strategies, too.
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Pneumonia and Heart Disease: What You Should Know - Healthline
Current and advanced therapies for chronic wound infection – The Pharmaceutical Journal
By daniellenierenberg
After reading this article, you should be able to:
A wound is any injury that disrupts the structure of healthy skin tissue caused by chemical, mechanical, biological or thermal trauma. Wounds can be classified as acute or chronic, depending on their period of healing[1]. Acute wounds usually heal without complication within ten days; however, chronic wounds do not undergo normal healing processes, commonly have exaggerated inflammation, persistent infections or microbial biofilm formation and persist longer than six weeks[24]. The most frequent causes of chronic wounds are pressure, diabetes and vascular diseases[5].
Chronic wounds are a global problem, with annual cases rising dramatically owing to the ageing population and increased prevalence of diabetes and obesity[6]. It is estimated that up to 7% of the UK adult population has a chronic wound, costing the NHS 8.3bn each year in staff costs, wound dressings and medication[7]. Individual costs for wound management have been reported to vary, from 358 to 4,684 per patient for a wound that follows the normal healing trajectory, increasing to 831 to 7,886 per patient for a chronic, non-healing wound[7]. The majority of the costs account for GP and nursing time, with infected wounds costing an additional 1.39bn on antibiotics[7].
Results from one study, published in 2020, found that 59% of chronic wounds healed if there was no evidence of infection, compared with 45% if infection was present or suspected[7].Health conditions, such as diabetes mellitus and vascular disease, can predispose people to wounds that are difficult to heal, which can become chronic unless the underlying causes are addressed. For example, people with diabetes are prone to have a high incidence of wounds on their feet, which are slow to heal because of the impact of diabetes on the immune system, circulation and diabetic neuropathy. Complex chronic wounds, such as venous leg ulcers and diabetic ulcers, can significantly impact quality of life, morbidity and mortality[7].
Wound healing is a complex series of physiological reactions and interactions between numerous cell types and chemical mediators[8,9]. It comprises four coordinated and overlapping phases: haemostasis, inflammation, proliferation and remodelling[10].
The Figure below shows the phases of wound healing[11].
The first stage, haemostasis, is instantly activated after injury to stop bleeding at the site and prevent the entry of pathogens. In primary haemostasis, within seconds of an injury occurring, damaged blood vessels vasoconstrict to reduce blood flow through the wound area and diminish blood loss. Platelets adhere to the sub-endothelium of the impaired vessels, initiated by the presence of von Willebrand factor. This binds to glycoprotein Ib receptors on the surface of platelets, causing a conformational change on the platelet surface, activating platelets. These activated platelets release chemicals, such as adenosine diphosphate,serotonin andthromboxane A2, from their dense granules to stimulate platelet recruitment and adhesion to form a platelet plug[12,13]. Secondary haemostasis is a sequence of events, described as a coagulation cascade, that consequently converts soluble fibrinogen into insoluble fibrin. A fibrin mesh sticks to the platelet plug producing a haemostatic plug to seal the inside of wound[12,14].
At the beginning of the inflammatory phase, activated platelets also release pro-inflammatory cytokines and growth factors to stimulate the recruitment of immune cells to clean the wound area, initially involving infiltration of neutrophils and monocytes[15]. Monocytes undergo a phenotypic change to become macrophages. The previously constricted blood vessels also vasodilate because of increased prostaglandins, facilitating the chemotaxis of inflammatory cells[16,17]. The proliferation phase is charactered by re-epithelialization, capillary regeneration and the formation of granulation tissue(18). Fibroblasts and endothelial cells proliferate during this phase, stimulated by the numerous cytokines and growth factors released by the platelets and macrophages. This leads to the formation of new blood vessels in a process called angiogenesis[18].
After migration to the wound site, fibroblasts begin to proliferate and synthesize collagen and extracellular matrix components, such as proteoglycans, hyaluronic acid, glycosaminoglycans, and fibronectin, to form granulation tissue[1618]. The final stage is remodelling, which can last for several years. The formation of new capillaries slows, facilitating maturation of blood vessels in the wound. Type III collagen is replaced by type I collagen in the extracellular matrix to create a denser matrix with a higher tensile strength. The differentiation of fibroblasts into myofibroblasts causes the wound to physically contract. However, owing to differences in collagen type, new tissue after healing does not fully regain its original strength[1618].
Delayed wound healing can be caused by local and/or systemic factors. Local factors in the wound site include oxygen deficiency (causing chronic hypoxia), excessive exudate (causing maceration) or insufficient exudate (leading to desiccation), local infection, foreign bodies intensifying the inflammatory response, repetitive trauma, pressure/shear, and impaired vascular supply to the injury area[16,19].
Systemic factors that delay the healing process include the following[16,19]:
Oestrogen insufficiency, for instance in postmenopausal women, is known to impair all stages of wound repair process, especially inflammation and regranulation, with improved wound healing being a potential benefit of hormone replacement therapy. Androgens can repress cutaneous repair in both acute and chronic wounds, retarding the healing process and increasing inflammation[20].
The process can also be delayed in people with immunocompromised conditions, such as acquired immunodeficiency syndrome, cancer and malnutrition, with deficiencies in protein, carbohydrates, amino acids, vitamins A, C and E, zinc, iron, magnesium all having an effect[16,19,21]. Certain medicines can also delay the process, such as glucocorticoid steroids, chemotherapeutic drugs and non-steroidal anti-inflammatory drugs[19,21].
The most common causes of delayed chronic wound healing are infection and biofilm formation: biofilms are microscopically identifiable in up to 60% of chronic and recurrent wounds,leading to significant morbidity and mortality and an escalated healthcare cost[5,22,23].
A wound is considered infected when there are sufficiently large numbers of microbes presenting in wound environment or sufficient virulence to raise either a local or systemic immune response.
The wound-infection continuum has three stages: contamination, colonisation and infection. In the contamination phase, micro-organisms are unlikely to replicate because of an unfavourable environment. Colonisation happens when microbes successfully multiply, but not in sufficient levels to destroy host defences. However, the accelerated loads and persistence of microbes in wound environments may prolong the inflammatory phase and delay wound healing. When bacteria invade deeper into the wound bed and proliferate speedily, they can provoke an immune reaction and initiate local infection. As pathogens proliferate beyond the boundaries of the wound, infection may spread into deeper tissues, adjacent tissues, fascia, muscle or local organs. Eventually, systemic infection, such as sepsis, can occur when microbes invade into the body via vascular vessels or lymphatic systems, affecting the entirety of the body[24,25].
Biofilm is an extracellular polymeric substance produced by bacteria that acts as a physical barrier, enveloping bacteria and protecting them from host defences and antimicrobial agents. Several pathogens isolated from chronic wounds are typically capable of forming biofilms, such asStaphylococcus aureusandPseudomonas spp[5,23,24,26]. Biofilms persisting within chronic wounds can continuously stimulate host immunity, resulting in the prolonged release of nitric oxide, pro-inflammatory cytokines such as interleukin-1 and TNF-, and free radicals, and activation of immune complexes and complement, causing the healing process to fail and convert to a chronic state[23,27]. Sustained inflammatory reactions also trigger an escalated level of matrix metalloproteases, which can disrupt the extracellular matrix[16].
Most of the time, wound infection is diagnosed via visual inspection based on clinical signs and symptoms, including the classic signs of heat, pain, swelling, suppuration, erythema and fever. Typical characteristics of an acute infected wound are pain, erythema, swelling, purulent drainage, heat and malodour. In addition, a chronic wound may display signs of delayed healing, wound breakdown, friable granulation, epithelial bridging and pocketing in granulation tissue, increasing pain and serious odour.
Microbiological analysis of a specimen from wound cultures (using tissue biopsy or wound swab, pus collection or debrided viable tissue) is performed to identify causative microorganisms and guide the choice of antimicrobial therapy. Traditional diagnostics can be time consuming, and some organisms can be difficult to culture, so molecular techniques including DNA sequencing may help with characterising genetic markers[25]. Other laboratory markers, such as C-reactive protein, have also been used as markers and imaging techniques, such as CT scanning and autofluorescence imaging, may help with real-time diagnosis[25,28].
In clinical practice, the evaluation and identification of underlying conditions that affect wound healing are vital to optimising wound care. Accurate assessment of causes and comorbidities will inform the best course of treatment, such as compression therapy for venous leg ulcers or offloading (relief of pressure points) for people with diabetic foot ulcers[29]. The underlying pathologies of wounds are numerous and failure to address them can lead to a failure in healing[2,29].
Once any underlying conditions are identified, the wound bed should be prepared to optimise the chance of healing. A wound hygiene approach should be considered; its core principle is to remove or minimise unwanted materials, such as biofilm, devitalised tissue and foreign debris, from the wound bed to kickstart the healing process[30]. A holistic patient and wound assessment will ensure wound pathology and wound biofilm are managed simultaneously[30]. The TIME framework (tissue, infection/inflammation, moisture balance, edges) is a systematic approach to wound management[31]. Wound-bed preparation and the TIME approach should be used alongside a holistic assessment of other patient factors such as pain, nutrition and hydration[2].
Effective management of infection in chronic wounds involves the removal of necrotic tissue, debris and biofilms using debridement plus the appropriate use of antimicrobials (including topical antiseptics and systemic antibiotics)[1,32].
Antiseptics have a broad spectrum of bactericidal activity and are used externally for the purposes of eliminating bacterial colonisation, preventing infection, and potentially stimulating wound healing. They are less likely to cause antimicrobial resistance (AMR) than antibioticsand inhibit the development of microbes by disrupting cell walls and cytoplasmic membranes, denaturing proteins, and damaging bacterial DNA and RNA[5,23,33,34]. An ideal antiseptic agent should have broad-spectrum activity, a fast onset of action, long-lasting activity, be safe for healthy surrounding tissue, possess minimal allergenicity, be stable in blood and tissue protein, persistently remain within the wound bed, and potentially be active against biofilms[23,35]. Antiseptics, antimicrobial washes or surfactants can be used to clean the wound and peri-wound skin and prepare the wound bed for debridement[30].
A variety of antiseptic agents are used in clinical practice[23,34]:
Antiseptics can also be used as an adjunct to other therapies (e.g. negative pressure therapies) in treating complicated wound types(e.g.diabetic foot ulcers,venous leg ulcers and sternal wounds)[36].
All open wounds will be colonised with bacteria, but antibiotic therapy is only required for those that are clinically infected[37]. Systemic antibiotic therapy should only be considered for the treatment of cellulitis, osteomyelitis, sepsis, lymphangitis, abscess, and invasive tissue infection. Inappropriate use of systemic antibiotics may increase the risk of side effects and contributes to emergence of AMR[5]. The choice of initial therapy and the duration is frequently empirical and should take into account the type of wound, severity of infection, suspected pathogens and local AMR[38]. With severe infections, broad-spectrum antibiotics should be used against both gram-positive and gram-negative organisms, while a relatively narrow spectrum agent is enough for most mild and many moderate infections[5].
A systematic review assessed the clinical and cost-effective efficacy of systemic and topical antibiotic agents in the treatment of chronic skin wounds. The authors of the review suggested that there was insufficient evidence to support any routine use of systemic antibiotics in specific chronic wounds[39].
Appropriate and judicious use of antimicrobials must be considered when managing wounds. The use of topical antibiotics is not recommended for eliminating bacterial colonisation or wound infections because of their limited effectiveness, high risk of resistance and potential to cause contact allergy[5,35].
AMR occurs when microorganisms naturally evolve in ways that cause medicines used to treat infections to become ineffective, and these micro-organisms become resistant to most[40,41]. The misuse and overuse of antibiotics is a major cause of the emergence of AMR, via four main mechanisms[42]:
Moreover, the multicellular nature of biofilm matrix is likely to give extra protection to bacteria communities, makes them resistant to antibiotics. There are several proposed mechanisms for AMR related to biofilm: the alteration of chemical environment within biofilm, slow or inadequate diffusion of the antibiotics into the biofilm, and a differentiated biofilm subpopulation[43].
Topical antimicrobial use plays an important role when the wound is clinically infected or there is a suspected biofilm. The British Society for Antimicrobial Chemotherapy and European Wound Management Association position paper highlighted antimicrobial stewardship (AMS) a set of strategies to improve the appropriateness and minimise the adverse effects of antibiotic use as being central to wound care treatment to improving patient outcomes, reducing microbial resistance and decreasing the spread of infections caused by multidrug-resistant organisms[37]. Effective AMS avoids the use of antimicrobial therapy when not indicated while enabling the prescribing of appropriate antimicrobial interventions when they are indicated to treat infection.
The UK government has outlined a 20-year vision for reducing AMR, proposing a lower burden of infection through better treatment of resistant infections[44]. This includes the optimal use of antimicrobials and good stewardship across all sectors and appropriate use of new diagnostics, therapies, vaccines and interventions in use, combined with a full AMR research and development pipeline for antimicrobials, alternatives, diagnostics, vaccines and infection prevention across all sectors.
The use of alternatives to traditional antibiotic therapy is of huge interest for combating increasing AMR, including bacteriophage therapy, phage-encoded products, monoclonal antibodies and immunotherapy[45]. Among these, endolysins phage-encoded peptidoglycan hydrolases selectively targeting bacterial taxa have been identified as promising antimicrobial agents because of their ability to kill antimicrobial-resistant bacteria and lack of reported resistance However, challenges restrict the widespread use of endolysin therapy, such as limited drug-delivery methods, their specificity to particular bacteria types, and bioavailability via IV administration[46,47].
Debridement is the physical removal of biofilm, devitalisedtissue, debris and organic matter and is a crucial component of wound care. The presence of non-viable tissue in the wound bed prevents the formation of granulation tissue and delays the wound healing process. The removal of non-viable tissue encourages wound healing. The type of tissue found in the wound bed (e.g. whether necrotic or sloughy) will determine whether debridement is required. Factors such as bioburden, wound edges and the condition of peri-wound skin can also influence whether debridement is required[48]. A range of techniques can be used, dependent on the clinicians ability level: these include autolytic, larval, mechanical, sharp and surgical methods[49,50].
The concept of moist wound healing is not newand can lead to healing up to 23 times quicker than that of dry wound healing[51,52].Wound dressings such as cotton wool, gauze, plasters, bandages, tulle or lint should not be used, as they do not promote a moist wound healing environment, require excessive changes, and can cause skin damage and pain during dressing changes. They have therefore been replaced by newer types of wound dressingsthat can play a role in autolysis and debridement, maintain a relatively stable local temperature, keep the wound hydrated, promote wound repair and prevent bacterial infection[14,53,54].
Wound dressings should keep the wound free from infections, excessive slough, contaminants and poisons, keep the wound at the ideal temperature and optimum pH for healing, be permeable to water, but not microbes, come away from wound trauma during dressing changes, not be painful and be comfortable[55]. There are a variety of dressings available for managing chronic wounds, such as hydrogels, hydrocolloids, alginates, foams, and film dressings[56]. Dressings can also be used carriers for active agents including growth factors, antimicrobial agents, anti-inflammatory agents, monoterpenes, silver sulfadiazine or silver nanoparticles[57].
Potential factors that may influence dressing selection include:
Antimicrobial dressings impregnated with iodine, silver and honey are available[58]. They can be divided into two categories: those that release an antimicrobial into the wound and those that bind bacteria and remove them from the wound into the dressing. A more detailed overview can be found in a recent consensus document on wound care and dressing selection for pharmacists[57].
It is essential wound dressings do not inadvertently lead to moisture-associated skin damage an umbrella term encapsulating incontinence-associated dermatitis, intertriginous dermatitis (or intertrigo), peri-wound maceration and peristomal dermatitis. Practitioners should ensure the dressing can manage any exudate and protects the peri-wound area. Skin barriers can be used to protect the peri-wound area and prevent skin damage[59].
Widely used to aid the healing of acute, chronic and traumatic wounds, negative-pressure wound therapy (NPWT) removes interstitial fluid/oedema and excessive exudate, provides a moist environment, improves blood flow and tissue perfusion, and stimulates angiogenesis and granulation tissue formation[4,60]. Results from several studies have demonstrated the selective effect of NPWT in eliminating non-fermentative gram-negative bacilli in wounds[36]. Additionally, NPWT can be combined with additional topical antimicrobial solutions, reducing bacteria load, stimulating wound closure and decreasing wound size faster than conventional NPWT[36,61,62].
Hyperbaric oxygen therapy wasfirst proposed as an additional treatment for chronic wounds in the mid-1960s. Treatment involves the intermittent exposure of the body within a large chamber to 100% oxygen at a pressure between 2.0 and 2.5 atmosphere absolute, leading to an increase in oxygen levels within haemoglobin and elevating oxygen tissue tension at the wound site[63].A Cochrane reviewpublished in 2015 reported a significant improvement in the healing of diabetes ulcers in the short term when treated with hyperbaric oxygen therapy. However, further high-quality studies are needed before clinical benefits can be proven[64].
For chronic wound healing, electrical stimulation is the most frequently studied biophysical therapy[4]. It uses direct current, alternative current, and pulsed current. Electrical stimulation has been shown to benefit every stage of the wound-healing process, both at cellular and systemic levels. During the inflammation phase, electrical stimulation promotes vasodilation and increases the permeability of blood vessels, thereby facilitating cellular movement to the wound site and so promoting a shorter inflammatory response.
Studies have reported an inhibition in bacterial proliferation after electric stimulation. In the proliferation phase, electrical stimulation raises the migration, proliferation and differentiation of endothelial cells, keratinocytes, myofibroblasts and fibroblasts. At the systemic level, it promotes revascularisation, angiogenesis, collagen matrix organisation, wound contraction, and re-epithelialisation. Ultimately,electrical stimulation promotes the contractility of myofibroblast and converts type III collagen into type I, along with rearranging collagen fibres to optimise the scars tensile strength[8,65,66].
A prospective clinical study conducted across the UK suggested that using an externally applied electroceutical device, combined with compression bandaging and dressings, was a cost-effective treatment for venous leg ulcers, compared with conventional treatments[67].
Low-frequency ultrasound has been used as an adjunct treatment for chronic wounds. It has a debriding effect, removing debris and necrotic tissue (primarily via cavitational and acoustic streaming phenomena). Ultrasound is also reported to disrupt biofilmin vitro, thus increasing the sensitivity of bacteria to antimicrobials[68]. It is proposed to be effective instimulating collagen synthesis, increasing angiogenesis,diminishing the inflammatory phase as well as promoting cellular proliferation[69].Several clinical studies have shown a reduction in wound size when wounds are treated with low-frequency ultrasound therapy[7072].
Extracorporeal shock wave therapy (ESWT) has been proposed to aid wound healing by transmitting acoustic pulsed energy to tissues. ESWT seems to promote angiogenesis, stimulate circulation, reduce anti-inflammatory response, and upregulate cytokine and growth-factor reactions[4]. A clinical trial demonstrated the feasibility and tolerability of ESWT in wounds with different aetiologies[73]. Furthermore, a review concluded that ESWT brings more benefits for patients with diabetic foot ulcers than hyperbaric oxygen therapy, based on increased angiogenesis, tissue perfusion and cellular reactions with reduced cell apoptosis, as well as a higher ulcer healing rate[74].
More recent developments include introducing nanomedicine to wound-healing approaches. It has been used to achieve controlled delivery, stimulate chronic wound healing and control microbial infections[14,75]. Nanotechnology-based wound dressings like nanogels and nanofibers offer a larger surface area and greater porosity, potentially enhancing absorption of wound exudate. They can also facilitate collagen synthesis and ultimately re-epithelisation through supporting the migration and proliferation of fibroblasts and keratinocytes.
Nanomedicines also seem to aid healing through molecular and cellular pathways[75]. For example, a methacrylated gelatin (MeGel)/poly(L-lactic acid) hybrid nanofiber synthesised has been reported to stimulate the recruitment and proliferation of human dermal fibroblasts, thereby promoting wound healing[76]. Nanoparticles can not only act as carriers of antimicrobial agents, they can also have an intrinsic antimicrobial effect[75,77,78]. In 2021, Qiu et al. successfully developed an antibacterial photodynamic gold nanoparticle (AP-AuNPs) that demonstrated antibacterial effects on both Gram-negativeEscherichia coliand Gram-positiveStaphylococcus aureus,as well as potentially inhibiting biofilm formationin vitro[79].
Growth factors such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) are down-regulated in chronic wounds, suggesting that topical administration of growth factors and cytokines could improve wound healing[80].
Growth factors can improve wound repair through several mechanisms[81]:
Growth factors that have been studied in wound healing are EGF, VEGF, FGF, PDGF, transforming growth factor-beta 1 (TGF-1) and granulocyte-macrophage colony stimulating factor[82]. Becaplermin (rhPDGF-BB) was the first growth-factor therapy approved by the US Food and Drug Administration, after it demonstrated effectiveness in treating complex wounds when combined with standard wound care[80]. A systematic review and meta-analysis indicated that growth factors were effective in healing venous stasis ulcers, increasing wound healing by 48.8% compared with placebo and showing no difference in adverse effects compared with controls[83].
Stem cells may have certain advantages in wound healing because of their ability to differentiate into specialised cells and secrete numerous mediators including cytokines, chemokines, and growth factors[84,85]. This makes them a promising approach for treating chronic wounds.
Mesenchymal stem cells can be extracted from bone marrow, adipose tissue, umbilical cord blood, nerve tissue, or dermis and used both systemically and locally[86]. They release growth factors that stimulate blood-vessel and granulation tissue formation, fibroblast and keratinocyte migration, collagen synthesis, and fibroblast activation, increase re-epithelialisation, exert immunomodulatory properties, regulate inflammatory responses, and display antibacterial activities[85,8789].
Many studies have investigated the efficacy of stem-cell therapies for a variety of wounds, including burns, non-healing ulcers, and critical limb ischemia[9096]. A systematic review published in 2020 that investigated the clinical application of stem-cell therapy for the treatment of chronic wounds showed the potential of a variety of stem cells in the restoration of impaired wound healing, bothin vitroandin vivo, despite the clinical evidence being very limited. As the recorded studies were on case-by-case basis, there is a lack of comprehensive guidelines for the use of stem cells in different wounds[97].
Auto-transplantationof adipose tissue-derived mesenchymal stromal cells has been proposed as a safe, alternative method to treat chronic venous ulcers[96]. Bioscaffold matrices comprising hyaluronic acid, collagen or other bio-polymeric materials have increasingly been applied for stem-cell transplantation. These matrices not only provide wound coverage, but also offer protection for stem cells and controlled delivery[86].
Skin equivalents are polymeric biomaterials increasingly adopted for both acute and non-healing ulcers, such as venous ulcers, diabetic foot ulcers or pressure ulcers, to temporarily or permanently substitute the structure and function of human skin. Skin substitutes are designed to increase wound healing, provide a physical barrier that protects the wound from trauma or bacteria, provide a moist environment for the repair process, replace impaired skin components and decrease morbidity from more invasive treatments like skin grafting[98,99].
They can usually be classified as one of three major types: dermal replacement, epidermal replacement, and dermal/epidermal replacement[98]. Epidermal replacements (substitutes) comprising isolated autogeneous keratinocytes cultured on top of fibroblasts include Myskin (Regenerys), Laserskin(Fidia Advanced Biopolymers) and Epicel(Genzyme Tissue Repair Corporation). Dermal replacements include Dermagraft (Smith and Nephew) and Transcyte(Shire Regenerative Medicine)[98].
Epidermal/dermal skin replacements (also called composite skin substitutes) contain both epidermal and dermal layers that mimic the histological structure of original skin. The bi-layered bioengineering skin Apligraf (Organogenesis) was the first living skin equivalent for the management of complex chronic wounds like diabetic foot ulcers and venous leg ulcers. It is made up of a dermal layer of human fibroblasts embedded in a bovine type I collagen matrix and an epidermal layer generated by human keratinocytes[100]. Some other commercial products of composite substitutes are OrCel(Forticell Bioscience) andPermaDerm(Regenicin)[98]. In general, the current high cost of such dressings and limited evidence on effectiveness restricts them from being widely adopted[101]. Recently, technologies such as electrospinning or 3D-printing have been used to fabricate skin substitutes. Electrospinning can create nanofibers with high oxygen permeability, variable porosity, a large, exposed surface area and a morphology similar to the extracellular matrix, making them interesting candidates for skin substitutes[102,103].
TheNational Wound Care Strategy Programme, which was implemented by NHS England in 2018, has made progress in reducing unwanted variation in care and addressing suboptimal wound care.
Through its workstreams, the involvement of stakeholders, patients and carers, and the publication of the core capabilities for educating a multi-professional workforce, wound care has become a national priority. There are still many challenges in the management of chronic wounds the complexity of wound environment, limited knowledge of the biological, biochemical, and immunological healing processes, and the increasing complexity of disease pathophysiology that comes with ageing populations.
The development of standardised and clinically relevant testing for wound dressings, along with high-quality clinical trials, would enable useful comparisons of treatments. The whole episode of care should be considered in assessments of the cost-effectiveness of different dressings and devices, rather the simple cost of the individual entity. All these complex concerns restrict success in wound management, which in turn negatively impacts the quality of life of the patients and places a burden on global healthcare systems[75,104]. Organisations and healthcare providers should share best practice and education of healthcare professionals is needed to get the best outcomes for patients with preventable chronic wounds.
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Current and advanced therapies for chronic wound infection - The Pharmaceutical Journal
Why do some women struggle to breastfeed? A UCSC researcher on what we know, and don’t – Lookout Santa Cruz
By daniellenierenberg
Have something to say? Lookout welcomes letters to the editor, within our policies, from readers. Guidelines here.
Like many moms, UC Santa Cruz stem cell biologist Lindsay Hinck struggled to make enough milk to feed her infant daughter.
Frustrated by her low supply, she went to a lactation consultant, who advised her to wake up every night at 3 a.m. an optimal time in the hormone cycle to pump precious drops of liquid gold for her baby.
Hinck did it, but she also wondered, why was she having so much trouble and losing so much sleep while other moms had no problem feeding their newborns?
After many exhausting early hours with the pump, Hinck did what she does best: research. She found something remarkable: More than 25% of women worldwide struggle to produce enough milk to feed their infant children.
But when she looked to scientific literature for an explanation, it came up empty.
Hinck, who got a masters degree in biochemistry from UC Davis and her Ph.D. in cancer biology from Stanford University, was shocked to realize scientists have barely studied human lactation. There was almost no information for scientists or moms about how human breast tissue makes milk.
Hinck decided to change that.
She switched her UCSC labs research focus from breast cancer to lactation, specifically looking into how stem cells in breast tissue create milk and why some womens supply comes out low.
Its a topic some view with skepticism; lactation and breastfeeding are still treated by many as uncomfortable or inappropriate. In fact, in the early days of her research, Hinck had to get funding from an animal health firm interested in increasing milk production in cows.
We sexualize breasts in the most amazing ways, and people dont seem to have a problem talking about that, says Hinck, who has been at UCSC since 1998 and serves as co-director of the universitys Institute for the Biology of Stem Cells. Yet when it gets down to their biological function which is to provide nutrition for infants somehow the world clams up.
With the a nationwide baby formula shortage having affected millions of families, Hincks work funded by the National Institutes of Health takes on even greater importance. Parents whose infants have allergies or metabolic conditions rely on formula, and women particularly those who are already struggling to breastfeed cant suddenly build a milk supply overnight when formula is not available.
Hinck spoke with Lookout from her office at UCSC; this interview has been edited for clarity.
Lookout: What is lactation insufficiency?
Lindsay Hinck: Lactation insufficiency is the inability of a woman to produce the breast milk in daily volumes that meet the nutritional needs of her infant.
The statistics that we have are very broad. Somewhere between 25% and 67% of women will experience this worldwide. And this statistic is so broad because lactation insufficiency is understudied, and its hard to study.
A lot of scientists would agree that breast milk does confer an immunological advantage, and that it is filled with immune cells that the mother is giving to her infant; milk is also filled with microbes. Those are two of the major deliveries to children that come through breast milk, not to mention all the comfort of the breastfeeding cycle, psychological comfort and connectedness through the skin on skin feeling of being fed that way.
Lookout: How do you feel about your research in the context of the baby formula shortage?
Hinck: A lot of women rely on formula because they have trouble building a milk supply. Currently there are no FDA (U.S. Food and Drug Administration)-approved drugs in the United States for lactation insufficiency. My research is identifying therapeutically relevant drug targets, so that maybe we will be able to address this issue. We hope that one day women can take a drug to better build a milk supply.
Were working on a nonhormonal drug. The current drugs work on the hormone prolactin, whereas my lab studies stem cells. None of the drugs targeting prolactin have been approved, because they have terrible side effects.
Hormones have wide-ranging effects. Theyre released and they spread throughout the body. I think maybe we have an opportunity to identify a therapeutic that wont have so many deleterious side effects.
(Mel Melcon / Los Angeles Times)
Lookout: Because of the baby formula shortage, an easy answer might be to tell mothers they should just breastfeed. Why might that not be a compassionate or realistic response?
Hinck: No, thats not a compassionate or realistic response. I mean, especially if you havent built your milk supply, its not a trivial thing. If you didnt build a milk supply from the beginning, and even if you are breastfeeding, if you cant meet the daily needs of your infant, you simply dont have the milk. Its just not there.
Building a milk supply doesnt occur over 24 hours, you cant just latch the child on more often and have more milk in a day. Eventually the milk supply will increase, but its complicated. Its hard for some women to initiate and build a milk supply.
Lookout: In the U.S., lactation and breastfeeding seem to be treated as somewhat taboo or uncomfortable topics. How do you respond to that?
Hinck: We dont want to see women doing it. It seems to make people uncomfortable, so at best we provide women a room somewhere, and at worst there are no accommodations. We certainly dont appear as a society that welcomes breastfeeding in public. I am bemused at this, and find it tragic at the same time.
I myself, when I breastfed, I just breastfed. I just got to the point where tough, you know? I know I made people uncomfortable. My mother-in-law would try to drape a huge blanket over me and my child in the summer in the heat, and it was like 100 degrees underneath that blanket. I would just be like, This is crazy! Its just an infant at my breast eating. Seems fine to me. And I dont think the climate has dramatically changed in many places in the world. My daughter is 22 years old, and in 22 years I have not seen that needle budge. It still seems like breastfeeding makes people uncomfortable, and I dont know why.
Lookout: Have you faced any skepticism about this as a research topic, or faced any particular challenges in studying lactation compared to other topics, like cancer?
Hinck: I would say that I have had a harder time getting my lactation research funded. But recently, I received a NIH grant from the National Institutes for Child Health and Human Development, so thats been terrific. There has been a gaining interest in a number of whats been classified as womens diseases that have been understudied for a long time.
But in the early days, I got money from an animal health firm because they were interested in increasing milk supply in cows. The biology is the same, however. So that worked out for me, and we were able to have a project that involves looking to see if this would work for building milk supply in cows, and then we were able to unravel the basic pathways, and now were applying that.
Lookout: What would you say are the big questions driving your current research?
Hinck: How does the breast tissue know how many progenitor cells to release or recruit to expand and to build the milk supply?
Breast stem/progenitor cells have to last a whole lifetime, and they have limited potential. Theyre stemlike in that they undergo an asymmetric cell division, which is a special type of cell division that recreates the stem/progenitor cells and gives rise to daughter cells that can go on to expand and become the milk producing cells.
So how many of those asymmetric cell divisions occur? How many cells are recruited to undergo those asymmetric cell divisions? All of that is unknown. Remember, the stem cell, the progenitor cell, wants to divide as infrequently as possible. Every time they replicate their DNA, it is opening up the possibility of damage that could lead to cancer.
Lookout: How would understanding these progenitor cell pathways help improve peoples lives, or pursue a solution to lactation insufficiency?
Hinck: Its early days. We dont understand a lot, and of course giving drugs to women who are pregnant is tough. There are drugs on the market for lactation domperidone is the best medicine to build milk supply, but its not approved by the FDA in America. It has side effects, cardiac side effects.
So its not unheard of that there would be drugs that could help build a milk supply. I think that would be the ultimate goal of our research, to understand if there is any pharmacological intervention that could help.
Lookout: What do you think nursing mothers who are struggling with lactation need? What can we do as a society to support them?
Hinck: Well, in the short term, certainly make workplace rules that change the climate. I mean, even if the rules are in place, if women dont feel welcome to take the breaks to pump then it doesnt happen. I mean, we all know how that goes.
Give mothers more time off. Create more welcoming environments when they come back to work to support them and their desire to breastfeed their child.
And in the longer term, we could understand the biology of building milk supply, which is still quite mysterious in humans. What are some of the factors that may impinge on that during pregnancy or after pregnancy?
Lookout: What did you have to do in order to feed your child when you were having trouble making enough milk?
Hinck: I saw the lactation consultant and I was told to pump at 3 a.m. when prolactin levels are the highest. I would set the alarm and get up and pump every night. I was also working full time, pumping every four hours. But I could barely pump the amount of milk for the next day.
Thats a burden, you know? Its just hard to balance. Youve got an infant, and youve got this other role, but youre also providing all the food for them. It doesnt always work seamlessly, thats for sure. I went to work to do my science, and I did the best I could.
It was a lot of work. Its so much to expect of mothers. And we just dont give parents, mothers, the space and time to breastfeed at work. Its also underappreciated that there could be other people who want to breastfeed, and we need to open doors for them for non-birth moms, trans people. Why do we keep lactation in just the realm of women? I think that if we understood lactation physiology better, we could help people breastfeed.
Guanan Gmez-Van Cortright is a 2022 graduate of the UC Santa Cruz Science Communication masters program. She has written for Good Times, KQED radio and the San Jose Mercury News.
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Why do some women struggle to breastfeed? A UCSC researcher on what we know, and don't - Lookout Santa Cruz
Bone Marrow Market Global Projection By Key Players AGendia, Agilent Technologies, Inc., Ambrilia Biopharma Inc Analysis and Forecast to 2028 …
By daniellenierenberg
This bone marrow market report provides details of new recent developments, trade regulations, import export analysis, production analysis, value chain optimization, market share, impact of domestic and localised market players, analyses opportunities in terms of emerging revenue pockets, changes in market regulations, strategic market growth analysis, market size, category market growths, application niches and dominance, product approvals, product launches, geographic expansions, technological innovations in the market. To gain more info on the bone marrow market contact Data Bridge Market Research for anAnalyst Brief,our team will help you take an informed market decision to achieve market growth.
The bone marrow market is expected to gain market growth in the forecast period of 2021 to 2028. Data Bridge Market Research analyses that the market is growing with the CAGR of 5.22% in the forecast period of 2021 to 2028 and is estimated to reach 13,899.60 USD Million by 2028. The growing amount of bone marrow diseases will help in escalating the growth of the bone marrow market. Bone marrow transplant also referred to as hematopoietic stem cell. It is a soft vascular tissue present in the interior of long bones. It comprises of two types of stem cells, that are hematopoietic and mesenchymal stem cells. Bone marrow is mainly responsible for the haematopoiesis, (formation of blood cells), production of lymphocytes, and the storage of fats. The bone marrow transplant is the last alternative generally recommended by the physicians in the cases of fatal bone marrow diseases and bone or skin cancer.
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Major factors that are boosting the growth of the bone marrow market in the forecast period are the growing of the incidences of non-Hodgkin and Hodgkin lymphoma, thalassemia, and leukemia, along with the common bone marrow diseases around the world, the developments in the technology and the enhancing of the healthcare infrastructure. Furthermore, the advancing signs of bone marrow transplant for heart and neuronal disorders, increasing funding in the logistic services and the growing per capita of the healthcare expenses are some of the other factors anticipated to further propel the growth of the bone marrow market in the coming years. However, the high expenditure for the treatment, shortage of the bone marrow donors and instability of the repayment are few of the factors further responsible for the impeding the growth of the bone marrow market in the near future.
Bone MarrowMarket Scope and Market Size
The bone marrow market is segmented on the basis of transplantation type, disease indication and end user. The growth amongst these segments will help you analyse meagre growth segments in the industries, and provide the users with valuable market overview and market insights to help them in making strategic decisions for identification of core market applications.
To Gain More Insights into the Market Analysis, Browse Summary of the Research Report@ https://www.databridgemarketresearch.com/reports/global-bone-marrow-market
Bone MarrowMarket Country Level Analysis
The bone marrow market is analysed and market size insights and trends are provided by country, transplantation type, disease indication and end user as referenced above. The countries covered in the bone marrow market report are the U.S., Canada and Mexico in North America, Germany, France, U.K., Netherlands, Switzerland, Belgium, Russia, Italy, Spain, Turkey, Rest of Europe in Europe, China, Japan, India, South Korea, Singapore, Malaysia, Australia, Thailand, Indonesia, Philippines, Rest of Asia-Pacific (APAC) in the Asia-Pacific (APAC), Saudi Arabia, U.A.E, South Africa, Egypt, Israel, Rest of Middle East and Africa (MEA) as a part of Middle East and Africa (MEA), Brazil, Argentina and Rest of South America as part of South America.
Europe dominates the bone marrow market because of the occurrence of the increasing number of innovative healthcare centers. Furthermore, the healthcare systems have introduced the bone marrow transplant in their contributions and the state-of-the-art public facilities which will further boost the growth of the bone marrow market in the region during the forecast period. North America is projected to observe significant amount of growth in the bone marrow market because of the growing cases of chronic diseases such as blood cancer. Moreover, the increasing of the geriatric population is one of the factors anticipated to propel the growth of the bone marrow market in the region in the coming years.
The country section of the bone marrow market report also provides individual market impacting factors and changes in regulation in the market domestically that impacts the current and future trends of the market. Data points such as consumption volumes, production sites and volumes, import export analysis, price trend analysis, cost of raw materials, down-stream and upstream value chain analysis are some of the major pointers used to forecast the market scenario for individual countries. Also, presence and availability of global brands and their challenges faced due to large or scarce competition from local and domestic brands, impact of domestic tariffs and trade routes are considered while providing forecast analysis of the country data.
Competitive Landscape and Bone MarrowMarket Share Analysis
The bone marrow market competitive landscape provides details by competitor. Details included are company overview, company financials, revenue generated, market potential, investment in research and development, new market initiatives, global presence, production sites and facilities, production capacities, company strengths and weaknesses, product launch, product width and breadth, application dominance. The above data points provided are only related to the companies focus related to bone marrow market.
The major players covered in the bone marrow market report are AGendia, Agilent Technologies, Inc., Ambrilia Biopharma Inc., Astellas Pharma Inc., diaDexus, Illumina, Inc., QIAGEN, F Hoffmann-La Roche Ltd, Sanofi, Stryker Corporation, PromoCell GmbH, STEMCELL Technologies Inc., Lonza, ReachBio LLC, AllCells, ATCC, Lifeline Cell Technology., Conversant bio, HemaCare, Mesoblast Ltd., Merck KGaA, Discovery Life Sciences., ReeLabs Pvt. Ltd., Gamida Cell, among other domestic and global players. Market share data is available for global, North America, Europe, Asia-Pacific (APAC), Middle East and Africa (MEA) and South America separately. DBMR analysts understand competitive strengths and provide competitive analysis for each competitor separately.
Browse the complete table of contents at https://www.databridgemarketresearch.com/toc/?dbmr=global-bone-marrow-market
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