So far, Bcells havent gotten the same attentionindeed, genetically engineered versions have never been tested in a human. Thats partly because engineering B cells is not that easy, says Xin Luo, a professor at Virginia Tech who in 2009 demonstrated how to generate B cells that have an added gene.

That early work, carried out at Caltech, explored whether the cells could be directed to make antibodies against HIV, perhaps becoming a new form of vaccination.

While that idea didnt pan out, now biotech companies like Immusoft, Be Biopharma, and Walking Fish Therapeutics want to harness the cells as molecular factories to treat serious rare diseases. These cells are powerhouses for secreting protein, so thats something they want to take advantage of, says Luo.

Immusoft licensed the Caltech technology and got an early investment from Peter Thiels biotech fund, Breakout Labs. Company founder Matthew Scholz, a software developer, boldly predicted in 2015 that a trial could start immediately. However, the technology the company terms immune-system programming didnt turn out to be as straightforward as coding a computer.

Ainsworth says Immusoft had to first spend several years working out reliable ways to add genes to B cells. Instead of using viruses or gene editing to make genetic changes, the company now employs a transposona molecule that likes to cut and paste DNA segments.

It also took time to convince the FDA to allow the trial. Thats because its known that if added DNA ends up near cancer-promoting genes, it can sometimes turn them on.

The FDA is concerned if you are doing this in a B cell, could you develop a leukemia situation? That is something that they are going to watch pretty closely, says Paul Orchard, the doctor at the University of Minnesota who will be recruiting patients and carrying out the study.

The first human test could resolve some open questions about the technology. One is whether the enhanced cells will take up long-term residence inside peoples bone marrow, where B cells typically live. In theory, the cells could survive decadeseven the entire life of the patient. Another question is whether theyll make enough of the missing enzyme to help stall MPS, which is a progressive disease.

Continued here:
A new gene therapy based on antibody cells is about to be tested in humans - MIT Technology Review

Bone Marrow Stem Cells Comments Off on A new gene therapy based on antibody cells is about to be tested in humans – MIT Technology Review | September 3rd, 2022

By Giles Campion, EVP, head of R&D and chief medical officer, Silence Therapeutics

siRNA is a gene-silencing technology with great potential for treating a wide range of rare diseases, as I discussed in my previous article, but its promise doesnt end there. In this last article in the series, I examine siRNAs potential for treating not-so-rare and even quite common diseases.

Unlike rare diseases, which are often caused by pathological genetic mutations, common diseases may be associated with genetic variants that are not pathological and therefore do not dysregulate a biological process. For example, variants of the LPA or PCSK9 gene can increase a persons risk of cardiovascular disease by affecting cholesterol levels, but these variants do not directly cause cardiovascular disease by disrupting a fundamental biological process. This contrasts with, for example, mutations in the HBB gene that cause beta thalassemia and disrupt the mechanisms that protect the body from toxic iron buildup.

Nevertheless, the approach to treating rare and common diseases with siRNA therapies is similar: silence a gene that has little or no effect on phenotypes outside the disease, thereby maximizing safety. This is an important factor in rare diseases, which often begin early in life and require lifelong treatment. But it is equally important in common chronic diseases, such as hyperlipidemia, in which a patient has abnormally high levels of fats in the blood, where patients may live for decades before they experience any overt symptoms from their condition and are not likely to tolerate a therapy with even minor side effects that interfere with their quality of life.

At the forefront of common conditions being targeted by gene silencing is elevated lipoprotein (a), or Lp(a), a cholesterol-rich particle closely related to the well-known cardiovascular risk factor LDL. High levels of Lp(a) are associated with high risk of cardiovascular events, such as heart attacks and strokes; low levels of Lp(a) are associated with a low risk of these events.

Unlike other types of cholesterol-carrying particles, Lp(a) levels are not significantly modifiable by lifestyle factors; levels are genetically determined by the variant of the LPA gene, which encodes apolipoprotein (a) a major protein component of Lp(a) that a person has. Because these variants are not pathological mutations, the person may not experience disease symptoms for years and may even be unaware of their elevated Lp(a) levels. Yet the condition is common: One in five people have high levels of Lp(a), defined as 50 mg/dl or 120 nmol/L. Other cholesterol-reducing medicines, such as statins, have no effect on Lp(a) and can even increase levels; currently there are no approved Lp(a)-reducing therapies.

However, assessments of human genetic databases, such as the UK Biobank, have revealed that cardiovascular risk is the only phenotype associated with Lp(a) levels. Some individuals have zero levels of Lp(a), and the only known phenotype in them is a much-reduced incidence of cardiovascular events. This indicates that silencing LPA with a properly designed siRNA therapy, such as Silences clinical-stage asset SLN360, could reduce the risk of cardiovascular disease in people with elevated Lp(a) while minimizing the risk of any unwanted or unexpected side effects.

The PCSK9 gene is another example of an siRNA target for the common condition of hyperlipidemia. The PCSK9 protein negatively regulates the cellular uptake of low-density lipoprotein-cholesterol (LDL-C) in the bloodstream by reducing the number of LDL receptors on the surface of cells. This means that high levels of PCSK9 decrease cellular uptake of LDL-C, leaving more of it in circulation.

High LDL-C levels in blood are associated with coronary artery disease (CAD). While not entirely determined by genetics, as Lp(a) levels are, some variants of the PCSK9 gene are associated with low levels of LDL-C and a reduced incidence of cardiovascular disease. Similar to the LPA gene, this suggests that silencing PCSK9 with an siRNA could reduce LDL-C levels in the blood to treat hyperlipidemia and reduce the risk of CAD. Indeed, the siRNA therapy inclisiran, which silences PCSK9, was approved by the European Union in December 2020 and in the United States in December 2021 for use in people with atherosclerotic cardiovascular disease (ASCVD), ASCVD risk equivalents, and heterozygous familial hypercholesterolemia (HeFH), in conjunction with lifestyle changes and other cholesterol-lowering medicines.

An important feature of siRNA therapies in the treatment of common chronic conditions such as elevated Lp(a) and elevated LDL-C is that they have long-lasting effects, and thus they require less frequent dosing than statins and other small molecule drugs, which must be taken daily. This in turn should increase patients compliance with the therapeutic regimen and thereby improve outcomes. In fact, a 2018 retrospective study found that hyperlipidemia patients who were prescribed the right intensity (level) of statin treatment and complied 100% with their therapy had a 40% lower risk of cardiovascular events than patients who received low-intensity statin treatment and had 5% compliance.1The study concluded that an optimal therapy could reduce the risk of cardiovascular events by 30% in three years.

Though published before any siRNA therapy was approved for hyperlipidemia, the studys implications are clear: Therapeutic intensity and patient compliance are important factors in saving peoples lives. With siRNA therapies, the intensity is known, and the compliance issues are likely to be less of an issue compared with oral drugs. This is just one aspect of siRNA that makes it as well-suited for treating common diseases as rare diseases.

siRNA also has the potential to improve outcomes in hematopoietic stem cell transplantation (HSCT). Though not a disease per se, HCST is a procedure commonly used to treat a range of blood cancers and, with increasing frequency, certain autoimmune disorders.

HCST involves ablating the existing bone marrow to make way for a healthy stem cell graft to repopulate the marrow. This ablation shifts an enormous load of dead iron-laden blood cells into the circulation. Retrospective studies suggest this acute release of toxic iron from ablated cells can adversely affect the survival of the stem cell graft and increase the risk of potentially lethal infections in HSCT patients.

As in the rare disease examples I mentioned previously, silencing TMPRSS6 with an siRNA could increase hepcidin to reduce iron levels in HSCT patients, potentially improving their survival and engraftment outcomes.

I am passionate about RNA technology and the benefits that targeted, precision siRNA medicines can bring to patients with rare diseases and not-so-rare diseases who need new therapeutic options. As both a physician and drug developer, I find it rewarding and exciting to witness this technology finally coming into its own, with the promise of delivering even greater benefits in the coming years.

Reference

About The Author:

Giles Campion, MD, joined Silence Therapeutics as head of R&D and chief medical officer in 2019 and was appointed as an executive director in 2020. He is an expert in translational medicine and an experienced biotech and pharmaceutical professional across many therapeutic areas, most recently in orphan neuromuscular disorders. He has held senior global R&D roles in several large pharma, diagnostics, and biotech companies, including as group vice president of the neuromuscular franchise at BioMarin Pharmaceutical Inc., and chief medical officer and senior vice president of R&D at Prosensa. He is also a co-founder of PepGen Ltd. He earned his bachelors and doctorate degrees in medicine from the University of Bristol and is listed on the General Medical Council (UK) Specialist Register (Rheumatology).

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The Promise Of Gene Silencing To Treat Not-So-Rare Diseases - BioProcess Online

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Pluripotent embyronic cell group giving rise to diverse cell lineages

Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineageincluding melanocytes, craniofacial cartilage and bone, smooth muscle, peripheral and enteric neurons and glia.[1][2]

After gastrulation, neural crest cells are specified at the border of the neural plate and the non-neural ectoderm. During neurulation, the borders of the neural plate, also known as the neural folds, converge at the dorsal midline to form the neural tube.[3] Subsequently, neural crest cells from the roof plate of the neural tube undergo an epithelial to mesenchymal transition, delaminating from the neuroepithelium and migrating through the periphery where they differentiate into varied cell types.[1] The emergence of neural crest was important in vertebrate evolution because many of its structural derivatives are defining features of the vertebrate clade.[4]

Underlying the development of neural crest is a gene regulatory network, described as a set of interacting signals, transcription factors, and downstream effector genes that confer cell characteristics such as multipotency and migratory capabilities.[5] Understanding the molecular mechanisms of neural crest formation is important for our knowledge of human disease because of its contributions to multiple cell lineages. Abnormalities in neural crest development cause neurocristopathies, which include conditions such as frontonasal dysplasia, WaardenburgShah syndrome, and DiGeorge syndrome.[1]

Therefore, defining the mechanisms of neural crest development may reveal key insights into vertebrate evolution and neurocristopathies.

Neural crest was first described in the chick embryo by Wilhelm His Sr. in 1868 as "the cord in between" (Zwischenstrang) because of its origin between the neural plate and non-neural ectoderm.[1] He named the tissue ganglionic crest since its final destination was each lateral side of the neural tube where it differentiated into spinal ganglia.[6] During the first half of the 20th century the majority of research on neural crest was done using amphibian embryos which was reviewed by Hrstadius (1950) in a well known monograph.[7]

Cell labeling techniques advanced the field of neural crest because they allowed researchers to visualize the migration of the tissue throughout the developing embryos. In the 1960s Weston and Chibon utilized radioisotopic labeling of the nucleus with tritiated thymidine in chick and amphibian embryo respectively. However, this method suffers from drawbacks of stability, since every time the labeled cell divides the signal is diluted. Modern cell labeling techniques such as rhodamine-lysinated dextran and the vital dye diI have also been developed to transiently mark neural crest lineages.[6]

The quail-chick marking system, devised by Nicole Le Douarin in 1969, was another instrumental technique used to track neural crest cells.[8][9] Chimeras, generated through transplantation, enabled researchers to distinguish neural crest cells of one species from the surrounding tissue of another species. With this technique, generations of scientists were able to reliably mark and study the ontogeny of neural crest cells.

A molecular cascade of events is involved in establishing the migratory and multipotent characteristics of neural crest cells. This gene regulatory network can be subdivided into the following four sub-networks described below.

First, extracellular signaling molecules, secreted from the adjacent epidermis and underlying mesoderm such as Wnts, BMPs and Fgfs separate the non-neural ectoderm (epidermis) from the neural plate during neural induction.[1][4]

Wnt signaling has been demonstrated in neural crest induction in several species through gain-of-function and loss-of-function experiments. In coherence with this observation, the promoter region of slug (a neural crest specific gene) contains a binding site for transcription factors involved in the activation of Wnt-dependent target genes, suggestive of a direct role of Wnt signaling in neural crest specification.[10]

The current role of BMP in neural crest formation is associated with the induction of the neural plate. BMP antagonists diffusing from the ectoderm generates a gradient of BMP activity. In this manner, the neural crest lineage forms from intermediate levels of BMP signaling required for the development of the neural plate (low BMP) and epidermis (high BMP).[1]

Fgf from the paraxial mesoderm has been suggested as a source of neural crest inductive signal. Researchers have demonstrated that the expression of dominate-negative Fgf receptor in ectoderm explants blocks neural crest induction when recombined with paraxial mesoderm.[11] The understanding of the role of BMP, Wnt, and Fgf pathways on neural crest specifier expression remains incomplete.

Signaling events that establish the neural plate border lead to the expression of a set of transcription factors delineated here as neural plate border specifiers. These molecules include Zic factors, Pax3/7, Dlx5, Msx1/2 which may mediate the influence of Wnts, BMPs, and Fgfs. These genes are expressed broadly at the neural plate border region and precede the expression of bona fide neural crest markers.[4]

Experimental evidence places these transcription factors upstream of neural crest specifiers. For example, in Xenopus Msx1 is necessary and sufficient for the expression of Slug, Snail, and FoxD3.[12] Furthermore, Pax3 is essential for FoxD3 expression in mouse embryos.[13]

Following the expression of neural plate border specifiers is a collection of genes including Slug/Snail, FoxD3, Sox10, Sox9, AP-2 and c-Myc. This suite of genes, designated here as neural crest specifiers, are activated in emergent neural crest cells. At least in Xenopus, every neural crest specifier is necessary and/or sufficient for the expression of all other specifiers, demonstrating the existence of extensive cross-regulation.[4] Moreover, this model organism was instrumental in the elucidation of the role of the Hedgehog signaling pathway in the specification of the neural crest, with the transcription factor Gli2 playing a key role.[14]

Outside of the tightly regulated network of neural crest specifiers are two other transcription factors Twist and Id. Twist, a bHLH transcription factor, is required for mesenchyme differentiation of the pharyngeal arch structures.[15] Id is a direct target of c-Myc and is known to be important for the maintenance of neural crest stem cells.[16]

Finally, neural crest specifiers turn on the expression of effector genes, which confer certain properties such as migration and multipotency. Two neural crest effectors, Rho GTPases and cadherins, function in delamination by regulating cell morphology and adhesive properties. Sox9 and Sox10 regulate neural crest differentiation by activating many cell-type-specific effectors including Mitf, P0, Cx32, Trp and cKit.[4]

The migration of neural crest cells involves a highly coordinated cascade of events that begins with closure of the dorsal neural tube.

After fusion of the neural fold to create the neural tube, cells originally located in the neural plate border become neural crest cells.[17] For migration to begin, neural crest cells must undergo a process called delamination that involves a full or partial epithelial-mesenchymal transition (EMT).[18] Delamination is defined as the separation of tissue into different populations, in this case neural crest cells separating from the surrounding tissue.[19] Conversely, EMT is a series of events coordinating a change from an epithelial to mesenchymal phenotype.[18] For example, delamination in chick embryos is triggered by a BMP/Wnt cascade that induces the expression of EMT promoting transcription factors such as SNAI2 and FoxD3.[19] Although all neural crest cells undergo EMT, the timing of delamination occurs at different stages in different organisms: in Xenopus laevis embryos there is a massive delamination that occurs when the neural plate is not entirely fused, whereas delamination in the chick embryo occurs during fusion of the neural fold.[19]

Prior to delamination, presumptive neural crest cells are initially anchored to neighboring cells by tight junction proteins such as occludin and cell adhesion molecules such as NCAM and N-Cadherin.[20] Dorsally expressed BMPs initiate delamination by inducing the expression of the zinc finger protein transcription factors snail, slug, and twist.[17] These factors play a direct role in inducing the epithelial-mesenchymal transition by reducing expression of occludin and N-Cadherin in addition to promoting modification of NCAMs with polysialic acid residues to decrease adhesiveness.[17][21] Neural crest cells also begin expressing proteases capable of degrading cadherins such as ADAM10[22] and secreting matrix metalloproteinases (MMPs) that degrade the overlying basal lamina of the neural tube to allow neural crest cells to escape.[20] Additionally, neural crest cells begin expressing integrins that associate with extracellular matrix proteins, including collagen, fibronectin, and laminin, during migration.[23] Once the basal lamina becomes permeable the neural crest cells can begin migrating throughout the embryo.

Neural crest cell migration occurs in a rostral to caudal direction without the need of a neuronal scaffold such as along a radial glial cell. For this reason the crest cell migration process is termed free migration. Instead of scaffolding on progenitor cells, neural crest migration is the result of repulsive guidance via EphB/EphrinB and semaphorin/neuropilin signaling, interactions with the extracellular matrix, and contact inhibition with one another.[17] While Ephrin and Eph proteins have the capacity to undergo bi-directional signaling, neural crest cell repulsion employs predominantly forward signaling to initiate a response within the receptor bearing neural crest cell.[23] Burgeoning neural crest cells express EphB, a receptor tyrosine kinase, which binds the EphrinB transmembrane ligand expressed in the caudal half of each somite. When these two domains interact it causes receptor tyrosine phosphorylation, activation of rhoGTPases, and eventual cytoskeletal rearrangements within the crest cells inducing them to repel. This phenomenon allows neural crest cells to funnel through the rostral portion of each somite.[17]

Semaphorin-neuropilin repulsive signaling works synergistically with EphB signaling to guide neural crest cells down the rostral half of somites in mice. In chick embryos, semaphorin acts in the cephalic region to guide neural crest cells through the pharyngeal arches. On top of repulsive repulsive signaling, neural crest cells express 1and 4 integrins which allows for binding and guided interaction with collagen, laminin, and fibronectin of the extracellular matrix as they travel. Additionally, crest cells have intrinsic contact inhibition with one another while freely invading tissues of different origin such as mesoderm.[17] Neural crest cells that migrate through the rostral half of somites differentiate into sensory and sympathetic neurons of the peripheral nervous system. The other main route neural crest cells take is dorsolaterally between the epidermis and the dermamyotome. Cells migrating through this path differentiate into pigment cells of the dermis. Further neural crest cell differentiation and specification into their final cell type is biased by their spatiotemporal subjection to morphogenic cues such as BMP, Wnt, FGF, Hox, and Notch.[20]

Neurocristopathies result from the abnormal specification, migration, differentiation or death of neural crest cells throughout embryonic development.[24][25] This group of diseases comprises a wide spectrum of congenital malformations affecting many newborns. Additionally, they arise because of genetic defects affecting the formation of neural crest and because of the action of Teratogens [26]

Waardenburg's syndrome is a neurocristopathy that results from defective neural crest cell migration. The condition's main characteristics include piebaldism and congenital deafness. In the case of piebaldism, the colorless skin areas are caused by a total absence of neural crest-derived pigment-producing melanocytes.[27] There are four different types of Waardenburg's syndrome, each with distinct genetic and physiological features. Types I and II are distinguished based on whether or not family members of the affected individual have dystopia canthorum.[28] Type III gives rise to upper limb abnormalities. Lastly, type IV is also known as Waardenburg-Shah syndrome, and afflicted individuals display both Waardenburg's syndrome and Hirschsprung's disease.[29] Types I and III are inherited in an autosomal dominant fashion,[27] while II and IV exhibit an autosomal recessive pattern of inheritance. Overall, Waardenburg's syndrome is rare, with an incidence of ~ 2/100,000 people in the United States. All races and sexes are equally affected.[27] There is no current cure or treatment for Waardenburg's syndrome.

Also implicated in defects related to neural crest cell development and migration is Hirschsprung's disease (HD or HSCR), characterized by a lack of innervation in regions of the intestine. This lack of innervation can lead to further physiological abnormalities like an enlarged colon (megacolon), obstruction of the bowels, or even slowed growth. In healthy development, neural crest cells migrate into the gut and form the enteric ganglia. Genes playing a role in the healthy migration of these neural crest cells to the gut include RET, GDNF, GFR, EDN3, and EDNRB. RET, a receptor tyrosine kinase (RTK), forms a complex with GDNF and GFR. EDN3 and EDNRB are then implicated in the same signaling network. When this signaling is disrupted in mice, aganglionosis, or the lack of these enteric ganglia occurs.[30]

Prenatal alcohol exposure (PAE) is among the most common causes of developmental defects.[31] Depending on the extent of the exposure and the severity of the resulting abnormalities, patients are diagnosed within a continuum of disorders broadly labeled Fetal Alcohol Spectrum Disorder (FASD). Severe FASD can impair neural crest migration, as evidenced by characteristic craniofacial abnormalities including short palpebral fissures, an elongated upper lip, and a smoothened philtrum. However, due to the promiscuous nature of ethanol binding, the mechanisms by which these abnormalities arise is still unclear. Cell culture explants of neural crest cells as well as in vivo developing zebrafish embryos exposed to ethanol show a decreased number of migratory cells and decreased distances travelled by migrating neural crest cells. The mechanisms behind these changes are not well understood, but evidence suggests PAE can increase apoptosis due to increased cytosolic calcium levels caused by IP3-mediated release of calcium from intracellular stores. It has also been proposed that the decreased viability of ethanol-exposed neural crest cells is caused by increased oxidative stress. Despite these, and other advances much remains to be discovered about how ethanol affects neural crest development. For example, it appears that ethanol differentially affects certain neural crest cells over others; that is, while craniofacial abnormalities are common in PAE, neural crest-derived pigment cells appear to be minimally affected.[32]

DiGeorge syndrome is associated with deletions or translocations of a small segment in the human chromosome 22. This deletion may disrupt rostral neural crest cell migration or development. Some defects observed are linked to the pharyngeal pouch system, which receives contribution from rostral migratory crest cells. The symptoms of DiGeorge syndrome include congenital heart defects, facial defects, and some neurological and learning disabilities. Patients with 22q11 deletions have also been reported to have higher incidence of schizophrenia and bipolar disorder.[33]

Treacher Collins Syndrome (TCS) results from the compromised development of the first and second pharyngeal arches during the early embryonic stage, which ultimately leads to mid and lower face abnormalities. TCS is caused by the missense mutation of the TCOF1 gene, which causes neural crest cells to undergo apoptosis during embryogenesis. Although mutations of the TCOF1 gene are among the best characterized in their role in TCS, mutations in POLR1C and POLR1D genes have also been linked to the pathogenesis of TCS.[34]

Neural crest cells originating from different positions along the anterior-posterior axis develop into various tissues. These regions of neural crest can be divided into four main functional domains, which include the cranial neural crest, trunk neural crest, vagal and sacral neural crest, and cardiac neural crest.

Cranial neural crest migrates dorsolaterally to form the craniofacial mesenchyme that differentiates into various cranial ganglia and craniofacial cartilages and bones.[21] These cells enter the pharyngeal pouches and arches where they contribute to the thymus, bones of the middle ear and jaw and the odontoblasts of the tooth primordia.[35]

Trunk neural crest gives rise two populations of cells.[36] One group of cells fated to become melanocytes migrates dorsolaterally into the ectoderm towards the ventral midline. A second group of cells migrates ventrolaterally through the anterior portion of each sclerotome. The cells that stay in the sclerotome form the dorsal root ganglia, whereas those that continue more ventrally form the sympathetic ganglia, adrenal medulla, and the nerves surrounding the aorta.[35]

The vagal and sacral neural crest cells develop into the ganglia of the enteric nervous system and the parasympathetic ganglia.[35]

Cardiac neural crest develops into melanocytes, cartilage, connective tissue and neurons of some pharyngeal arches. Also, this domain gives rise to regions of the heart such as the musculo-connective tissue of the large arteries, and part of the septum, which divides the pulmonary circulation from the aorta.[35]The semilunar valves of the heart are associated with neural crest cells according to new research.[37]

Several structures that distinguish the vertebrates from other chordates are formed from the derivatives of neural crest cells. In their "New head" theory, Gans and Northcut argue that the presence of neural crest was the basis for vertebrate specific features, such as sensory ganglia and cranial skeleton. Furthermore, the appearance of these features was pivotal in vertebrate evolution because it enabled a predatory lifestyle.[38][39]

However, considering the neural crest a vertebrate innovation does not mean that it arose de novo. Instead, new structures often arise through modification of existing developmental regulatory programs. For example, regulatory programs may be changed by the co-option of new upstream regulators or by the employment of new downstream gene targets, thus placing existing networks in a novel context.[40][41] This idea is supported by in situ hybridization data that shows the conservation of the neural plate border specifiers in protochordates, which suggest that part of the neural crest precursor network was present in a common ancestor to the chordates.[5] In some non-vertebrate chordates such as tunicates a lineage of cells (melanocytes) has been identified, which are similar to neural crest cells in vertebrates. This implies that a rudimentary neural crest existed in a common ancestor of vertebrates and tunicates.[42]

Ectomesenchyme (also known as mesectoderm):[43] odontoblasts, dental papillae, the chondrocranium (nasal capsule, Meckel's cartilage, scleral ossicles, quadrate, articular, hyoid and columella), tracheal and laryngeal cartilage, the dermatocranium (membranous bones), dorsal fins and the turtle plastron (lower vertebrates), pericytes and smooth muscle of branchial arteries and veins, tendons of ocular and masticatory muscles, connective tissue of head and neck glands (pituitary, salivary, lachrymal, thymus, thyroid) dermis and adipose tissue of calvaria, ventral neck and face

Endocrine cells:chromaffin cells of the adrenal medulla, glomus cells type I/II.

Peripheral nervous system:Sensory neurons and glia of the dorsal root ganglia, cephalic ganglia (VII and in part, V, IX, and X), Rohon-Beard cells, some Merkel cells in the whisker,[44][45] Satellite glial cells of all autonomic and sensory ganglia, Schwann cells of all peripheral nerves.

Enteric cells:Enterochromaffin cells.[46]

Melanocytes and iris muscle and pigment cells, and even associated with some tumors (such as melanotic neuroectodermal tumor of infancy).

Originally posted here:
Neural crest - Wikipedia

Cardiac Stem Cells Comments Off on Neural crest – Wikipedia | September 3rd, 2022

Rise In Research And Development Projects In Various Regions Such As East Asia, South Asia Are Expected To Offer An Opportunity Of US $ 0.5 Bn In 2022-2026 Period.

Fact.MR A Market Research and Competitive Intelligence Provider: The global induced pluripotent stem cell (iPSC) market was valued at US $ 1.8 Bn in 2022, and is expected to witness a value of US $ 2.3 Bn by the end of 2026.

Moreover, historically, demand for induced pluripotent stem cells had witnessed a CAGR of 6.6%.

Rise in spending on research and development activities in various sectors such as healthcare industry is expected to drive the adoption of human Ips cell lines in various applications such as personalized medicine and precision.

Moreover, increasing scope of application of human iPSC cell lines in precision medicine and emphasis on therapeutic applications of stem cells are expected to be driving factors of iPSC market during the forecast period.

Surge in government spending and high awareness about stem cell research across various organizations are predicted to impact demand for induced pluripotent stem cells. Rising prevalence of chronic diseases and high adoption of stem cells in their treatment is expected to boost the market growth potential.

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Besides this, various cells such as neural stem cells, embryonic stem cells umbilical cord stem cells, etc. are anticipated to witness high demand in the U.S. due to surge in popularity of stem cell therapies.

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Many key players in the market are increasing their investments in R&D to provide offerings in stem cell therapies, which are gaining traction for the treatment of various chronic diseases.

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Rise In Number Of CROS In Various Regions Such As Europe Is Expected To Fuel The Growth Of Induced Pluripotent Stem Cell Market At An Impressive CAGR...

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Healthy fasting is therapeutic if appropriately done, and evidence supports this. Our body can cure itself if given the correct nourishment, movement, sleep, emotional wellness, and surroundings; fasting boosts its curing capabilities. Its vital for holistic health.

It has beneficial effects on physical, emotional, brain, and spiritual health. In fact, it exists as a practice in most religions (religious fasting). For example, Muslims reduce caloric intake for a period of time during Ramadan to cleanse the mind, body, and soul. Other religious fasts include Christians, Greek Orthodox Christians, Jews, Hindus, and Buddhists, reducing caloric intake on certain days of the week or year.

Fasting has been performed for millennia with favorable effects, but only lately have studies shown its significance in adaptive cellular responses that minimize oxidative damage and inflammation, optimize energy metabolism and heart health, and bolster cellular defense. Furthermore, it helps with weight loss because it depletes liver glycogen, causing lipolysis and ketone body production, which reduces body fat (fat percentage) and hip circumference.

Fasting is such a popular scientific research topic today that the number of these studies demonstrating how good it is for holistic health keeps growing. The outcomes of these studies show that it can make you smarter, increase longevity by slowing down the aging process, and heal diseases, digestive issues, neurodegenerative disorders, and neurological disorders (mood disorders). Other health effects include the prevention of cardiovascular disease and chronic diseases.

Fasting activates our inner intelligence via calorie restriction. Its straightforward science. Fasting lets the digestive system rest by halting calorie intake. This break saves energy that would have gone toward digesting food. This conserved energy is used for repair, recovery, development, rejuvenation, and healing, which are needed for curing every human disease.

What happens first when were sick? Reduced appetite. So, what does this tell us? Our body reduces appetite to save energy that would have gone to digestion for mending and repair instead. Fasting does the same thing. It activates good genes with protective mechanisms, such as the SIRT1 gene, which regulates longevity, inflammation, fat and glucose metabolism, and other health effects.

A PLOS One study found that fasting reduces hunger hormones, improves metabolism, and helps people lose weight. Chicago researchers tested intermittent fasting on 20 obese adults for eight weeks. It enhanced the participants insulin resistance and glucose regulation, reduced cravings, and increased the feeling of fullness. Furthermore, they felt better overall and experienced no side effects.

Most people today overeat by incessantly munching and nibbling. Constant and excessive eating and out-of-balance dietary intake can overload the digestive system, leading to illness and a majority of health-related problems. Fasting helps mend this damage.

Chronic fasting (long-term fasting) enhances the lower eukaryote lifetime by altering metabolic and stress resistance pathways. Intermittent fasting (short-term fasting) protects against diabetes, malignancies, heart disease, neurodegeneration, obesity, hypertension, asthma, and rheumatoid arthritis.

Most people fast by only drinking water, dubbed water fasting. Other versions include juice fasting (apple cider vinegar, lemonade, carrot juice, celery juice, etc.) and eating light, where participants primarily eat vegetables, fruits, and lean meats like fish and chicken. However, real fasting involves going without food, solid, and liquid (aside from water) for at least 12 hours.

Several variations exist. Sometimes spiritual disciplines like prayer and meditation are included, turning it into a ritual. These disciplines make the process easier by calming the psyche.

As mentioned, various methods (diets) exist; all deliver positive effects. Here are a few examples:

This is the most common style of fasting and the most accurate form. Except for water, no solids or liquids are consumed. For those doing an extended water fast (over three days), sometimes herbal teas, tonics, and broths are consumedbut absolutely no caffeine or alcohol.

People following this diet will only drink vegetable and fruit juices for the duration of the fast.

This variation allows anything liquid, like broth or pureed soups, smoothies, and juices.

Its odd to call this one a fast because you can eat. Nevertheless, this diet is for people looking to purify their bodies. They must eliminate all non-plant-based foods (only things like fruits, vegetables, nuts, seeds, and legumes are allowed).

Skipping meals regularly, known as intermittent fasting or partial fasting, is becoming increasingly popular worldwide. People realize its physical and mental health benefits. It enhances energy, moods, sleep, and sex life. However, it involves a set daily fasting time.

Intermittent fasting also has the following benefits:

There are over twenty variations of intermittent fasting. The most popular include:

This strategy entails daily periods of fastingof 18 hours and then eating a light meal every other day. On alternate days you can eat healthy things like vegetables, berries, nuts, lean protein, etc.

Every day, you consume within specific periods of time. For example, your daily fast may be limited to eating from midday to 8:00 p.m..

You follow a schedule of regular eating for five days, then two days of fasting (preferably water fasting).

This fast allows one meal a day, but not breakfast. It is also commonly referred to as the One Meal a Day diet (OMAD).

You designate a six-hour window per day in which you can eat.

Most people fast to shed weight, regulate blood sugar, cleanse themselves of toxins, or regain mental clarity and emotional stability. However, it is a difficult thing to do alone. For those that need a little motivation, inspiration, and guidance, there are many fasting or detox retreats worldwide.

In addition, a growing number of medical clinics are offering guided fasting treatments. During these rehabilitation sessions, physicians supervise patients while undertaking water-only or very low-calorie (less than 200 kcal/day) fasting periods of one week or more. People participate for help in weight management or disease treatment and prevention.

Mexico has fasting pods, aka Fast incubators. These locations surround individuals with nature and block out food odors and noise. One can fast for 10 to 30 days. As a result, various disorders have reportedly healed faster. Many even experience improved eyesight and hearing.

While fasting is a simple concept, it can perplex many people due to the abundance of claims, methods, and precautions floating around the internet. However, it does not have to be challenging. On the contrary, it should be second nature to us.

Circadian rhythm fasting is the most natural and realistic technique to fast. In laymans terms, sunset to sunrise fasting involves eating ones last meal of the day early (near to or with sundown) and breaking it after sunrise. This provides for a minimum of 12-hour fasting and is one of the most efficient strategies to incorporate the practice into your lifestyle.

If you are still not hungry after 12 hours, gently extend your fast until you experience actual physical hunger, and then break youre fast correctly. You are not required to have breakfast if you arent hungry. Not feeling hungry in the morning indicates that your body is still detoxifying and processing your evening meal. Respect your body by fasting accordingly.

Fasting while sleeping is ideal since all critical detoxification, repair, and recovery processes occur during deep sleep. Our bodies detoxify at night, and the physical health benefits are more noticeable when fasting.

When you want to break the fast, however, it is entirely up to you and the signs your body is sending. Some people wake up hungry, while others do not till the afternoon. Pay attention to your body. There is a distinct distinction between fasting and starvation. If you are not hungry, respect your hunger and continue your fast for a few more hours.

Breaking a fast gently awakens your digestive system. So, gorging after a fast is terrible. It could overwhelm your stomach. Water breaks a dry fast best. Take a few sips, then eat fruit or 1-2 fresh dates. After 30-40 minutes, cook a wholesome meal. This is particularly important for long fasts.

Some fasters drink tea, coffee, or juice. Acidic drinks can damage stomach linings. Therefore, one should fast appropriately or not at all. If opting for juice fast, stick with vegetable juice like celery, green juice, or non-acidic fruits. Likewise, teas should be caffeine-free and herbal only (lavender, jasmine, etc.).

Theres no one-size-fits-all answer. Some find fasted workouts beneficial, while others find them hazardous. Fasted workouts depend on objectives, energy and hunger levels, training, and health conditions. However, do it if you can because fasted workouts are fantastic for insulin resistance, weight loss, and abdominal fat.

Note: Your body needs time to acclimate to a fast before you experience mental changes. You may get headaches or discomfort early on. Your brain is granted a cleaner bloodstream after your body eliminates toxins. This improves your thoughts, emotions, memory, and other senses.

Fasting causes ketogenesis, promotes potent changes in metabolic pathways and cellular processes such as stress resistance, lipolysis, and autophagy, and can have medical applications that are as effective as approved drugs, such as dampening seizures and seizure-associated brain damage, alleviating rheumatoid arthritis, and maximizing holistic health, as explained in the rest of this page.

Fasting uses up excess carbohydrates. The body burns fat. The metabolic rate rises, unlike with caloric restrictionweight loss results.

Half of our energy goes into digestion. This energy can be used to heal and regenerate, which happens during a fast. The human body recognizes what needs mending.

Sick and weaker cells are killed after 24-36 hours via apoptosis and autophagy, then recycled into new cells. Its natural. Apoptosis kills 50 to 70 billion human cells daily. Fasting boosts this rate.

Stem cell production and activation rise after fasting. The number of new stem cells and HGH peak during days 3-5 of a fast, then fall. Additional research shows that new white blood cells are created with increased stem cell growth, boosting the immune system.

Besides fat burning and strengthening the immune system, it reduces inflammation, rebalances the gut microbiome and hormones, protects the brain from neurological diseases, reduces cancer risk, slows aging, and promotes cell maintenance and repair.

Fasting is the best medicine, and its free!

Fasting has many powerful benefits, but its not for everyone. It should be avoided or done only under medical supervision in the following situations. People who are:

If you think you can do it, go for it! Fasting is the bodys natural stem cell therapy, renewing and regenerating the body. It is the ultimate biohack. Theres no better method to restore cells, improve healing, and increase energy and focus.

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Discover the Mental and Physical Health Benefits of Fasting - Intelligent Living

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Correlation between PSC differentiation potential and level of CHD7 expression

The potential to differentiate is a critical feature of PSCs used for cell transplantation therapy. Therefore, establishing an assay to evaluate differentiation potential is essential for the maintenance culture of PSCs. EB formation in EB assays is used as a minimum requirement to demonstrate differentiation potential, although EB formation assays may not necessarily guarantee the ability to differentiate into the designated target cells without bias. We used ESC H9 cells in the majority of experiments shown in this study as a representative PSC cell line to minimize the concern of clonal variance in PSC clones that is typically observed among iPSC clones generated from somatic cells with various genetic and epigenetic profiles and with versatile reprogramming methods. H9 cells cultured on VTN-Ncoated dishes with Es8 (Thermo Fisher) medium formed a considerable number of EBs; however, the number of EBs was reduced considerably after the cells were transferred to RFF2 medium and cultured for 15days (3days/passage5). The cells showed an ability to form a comparable number of EBs again when transferred to Es8 and cultured for 24days (3days/passage8 passages), consistent with our previous report using ESC KhES-1 and iPSC PFX#91. The expression level of CHD7 determined by flow cytometry and the copy number of CHD7 measured by ddPCR was higher in cells cultured with Es8 than in cells cultured with RFF2 (Fig.1A). We noted that the cell number scored at day 3 was approximately 3 times higher in cells cultured with Es8 than with RFF2. There was a positive relationship between cell growth rate, CHD7 expression level, and differentiation potential when H9 cells were cultured on VTN-Ncoated dishes and passaged in a single-cell suspension.

The differentiation potential of cells in culture can be altered by culture medium. (A) H9 cells cultured with Essential 8 (Es8) medium on vitronectin-N (VTN)coated dishes were transferred to RFF2 medium, cultured for 15days (3days/passage5 passages), transferred again to Es8 medium, cultured 24days (3days/passage8 passages), and then transferred again to RFF2 medium. Photos of cells in designated culture conditions, with the cell number scored at day 3 after seeding 1.0105 cells (left panels); flow cytometric analysis of CHD7, CHD7 copy numbers from 5ng total RNA at day 3 (middle panels); and photographs of EBs formed by day 14 from cells in each culture condition and numbers of EBs formed (right panels). The results are representative of three independent experiments. (B) H9 cells were cultured either with Es8 or RFF2 on VTN-Ncoated dishes. The loci of copy number variants (CNVs) detected when cells were cultured with Es8 medium (left panels) or RFF2 medium (right panels) are shown. CHD7 expression was determined by flow cytometry (mean values are shown), and CHD7 copy numbers were determined by digital droplet PCR in cells cultured with Es8 or RFF2 medium.

We next explored the mechanisms through which cells had altered CHD7 expression levels and the ability to form EBs by simply changing the culture medium. There were at least two possible explanations for this mechanism. First, cells in culture might exhibit alterations in both CHD7 expression and the resultant differentiation potential because of signals initiated and mediated by certain factors in the medium. Alternatively, CHD7 expression levels might be genetically and epigenetically predetermined in individual cells and might not be regulated or changed by signals triggered by factors in the culture medium. In the latter case, CHD7 expression levels in cultured cells might change if different dominant cell populations were selected based on a growth advantage in a new culture medium. To evaluate these possible mechanisms, cells in the culture were marked by their CNVs so that changes in the dominant cell population could be detected by comparing CNV profiles. H9 cells cultured with Es8 medium were transferred to RFF2 medium and then were placed back in Es8 medium, and the CNV profiles of H9 cells were examined and compared. Notably, the CNV profiles of cells cultured with Es8 medium included CNVs at loci 4q22.1, 8q23.1, 16p11.2, and Xq26.1, whereas cells cultured with RFF2 medium had CNVs at none of these loci. Additionally, cells cultured with RFF2 medium contained CNVs at the specific locus 14q32.33, and these CNVs were not detected in cells cultured with Es8 medium, indicating that the cell population cultured with Es8 medium was different from that cultured with RFF2 medium (Fig.1B). This observation led us to explore the mechanisms through which certain cell populations could be selected to expand under specific culture conditions.

Next, we explored the impact of cell culture medium on the metabolic systems of cultured cells. The major metabolic pathway used by PSCs and cancer cells is the glycolytic pathway7, which is coupled with suppression of mitochondrial activity, as reflected by a low mitochondrial membrane potential (M) and reduced ROS in the mitochondria8,9. We found that the majority of cells cultured with Es8 medium did not show marked ROX staining, which was used to detect ROS produced by mitochondrial activity; the exception was that cells along the rims of colonies did show ROX staining. Furthermore, JC-1 assays showed a suppression of mitochondrial membrane voltage, suggesting that there was no marked mitochondrial activity by day 3 of culture (Fig.2A). In contrast, cells cultured with RFF2 showed marked ROX staining in most cells and an activated mitochondrial membrane potential by the JC-1 assays, suggesting activated mitochondrial function in cells cultured with RFF2 (Fig.2A). RFF2 medium contained high concentrations (approximately 23mg/mL) of protein and various amino acids in addition to moderately high glucose (2.52g/L), which could support mitochondrial function. However, Es8 medium contained high glucose (3.1g/L) and a limited amount of amino acids. Thus, Es8 medium could support the glycolytic pathway and at the same time limit the activation of mitochondrial function. The suppressed mitochondrial membrane voltage of cells cultured with Es8 medium supported this idea. There was a reciprocal relationship between the expression of CHD7 and mitochondrial function when cells were maintained in an undifferentiated state (Fig.2A). Metabolic analysis showed that the RFF2 culture medium contained malate and citrate as a result of activation of the tricarboxylic acid cycle in cells, whereas the Es8 culture medium did not (Fig.2B), consistent with the above argument. Furthermore, 2-aminoadipic acid (2-AAA) was detected in the RFF2 medium but not in the Es8 medium (Fig.2B), indicating that the kynurenine catabolic pathway, which leads to loss of an undifferentiated state and initiation of ectoderm differentiation6, was activated in cells cultured with RFF2. This observation suggested that some cells cultured with RFF2 exhibited activated mitochondrial function and underwent spontaneous differentiation, but could not be maintained in RFF2 as this medium lacked the factors necessary to support differentiated cells, and therefore these cells died. Thus, only undifferentiated cells with mitochondrial activation below the permissible level not to undergo differentiation could be cultured and maintained with the RFF2 medium. A positive correlation between the activation of mitochondrial membrane voltage and the initiation of differentiation, as suggested by the secretion of 2-AAA, was observed during the culture of cells with RFF2. This observation was supported by additional experiments; namely, H9 cells cultured with Es6 medium depleted of basic fibroblast growth factor and transforming growth factor 1 compared with Es8 medium showed both an initiation of ectodermal differentiation, as demonstrated by gene expression profiling using RT-qPCR (Fig.2C, Fig. S1), and an elevated mitochondrial membrane voltage (Fig.2A,C). Thus, there is evidence that the activation of mitochondrial function is coupled with the initiation of differentiation processes. Next, we examined the impact of elevated CHD7 expression levels and the induction of spontaneous differentiation by introducing mCHD7 into undifferentiated cells.

Activation of mitochondrial function is coupled with differentiation. (A) Morphology, CellROX (ROX) immunostaining, CHD7 copy numbers, and mitochondrial membrane voltage (JC-1 assays) in cells cultured with Es8 medium on VTN-Ncoated dishes (Es8/VTN) for 3days (left panels) or with RFF2 medium on VTN-Ncoated dishes (RFF2/VTN) for 3days (right panels) are shown. Mitochondrial membrane voltage was assessed by subtracting baseline electrons (after depolarization) from total electrons (red circle). The percentage of each fraction in the scatter plot of JC-1 assays is shown. (B) H9 cells were cultured with Es8 or RFF2 medium, and culture medium was collected and replaced with fresh medium every day for 3days. 2-Aminoadipic acid (2-AAA), malate, and citrate levels in culture medium were measured using LCMS/MS. The measured values were standardized as the mean area ratio/cell/h for 3days. The average values (n=3) with error bars (SD) are shown in the bar graphs. The results of three independent experiments are shown. (C) Morphology, ROX staining, mitochondrial membrane voltage (JC-1 assays; red circle), and gene expression profiles (RT-qPCR score card panels) of H9 cells cultured with Es8 medium on VTN-Ncoated dishes on day 5 (left panel: starting material for differentiation by Es6 medium) and Es6 medium on VTN-Ncoated dishes on day 5 are shown (right panel). The interpretation of gene expression levels by RT-qPCR is shown in the attached table. The results of three independent experiments are shown.

There was a positive correlation between the level of CHD7 expression in undifferentiated cells and the differentiation potential manifested by the number of EBs formed in the EB formation assay (Fig.1A). Interestingly, mCHD7 induced differentiation of the three germ layers simultaneously, as determined by RT-qPCR in cells cultured with both Es8 and RFF2 media (Fig.3A, Fig. S2), suggesting a positive role of CHD7 in both endodermal and mesodermal differentiation processes as well as in ectodermal development. Furthermore, this suggested that there is an upper permissible level of CHD7 being in an undifferentiated state. Es8 and RFF2 media are designed to support the proliferation of undifferentiated cells, not differentiated cells, and cells that forced to differentiate following the introduction of mCHD7, could not be maintained in these culture media. Consequently, the number of cells to form EBs was markedly reduced after introduction of mCHD7 (Fig.3A). Moreover, the introduction of siCHD7 reduced the differentiation potential of cells cultured with Es8, as reflected by the marked reduction in the number of EBs formed (Fig.3A). The introduction of siCHD7 to cells cultured with RFF2 further reduced the level of CHD7 and naturally led to no or few EBs being generated. These results provided evidence for the observation in Fig.1A, demonstrating that the differentiation potential of undifferentiated cells correlated with CHD7 expression.

CHD7 expression affected the differentiation potential and growth of undifferentiated cells. (A) H9 cells cultured with Es8 on VTN-Ncoated dishes (Es8/VTN, left panels) or with RFF2 on VTN-Ncoated dishes (RFF2/VTN, right panels) were transfected with mock (control), mCHD7, or siCHD7. The morphology, CHD7 copy numbers, gene expression profiles (RT-qPCR), EB morphology, and EB numbers formed at day 14 under different culture conditions are shown. The representative results of three independent experiments are shown. (B) CHD7 expression in H9 cells determined by flow cytometry after cells were transferred from RFF2 to Es8 on VTN-Ncoated dishes at passage 0 (P0), P5, and P7. Cells were cultured for 3days between passages. (C) Fold increase of H9 cells after 48h (upper panel) and CHD7 expression, as determined by RT-qPCR, after transfection of H9 cells with various doses of siCHD7 (lower panel). The average values (n=3) with error bars (SD) are shown in the bar graphs. Representative data from three independent experiments are shown.

It is interesting to note that both the increased expression of mCHD7 and the activation of mitochondrial function induced differentiation. Therefore, there must be a reciprocal relationship between these events in cells in an undifferentiated state. In other words, cells with activated mitochondrial function need to express a limited level of CHD7 to grow in an undifferentiated state at the expense of having a reduced differentiation potential, whereas cells with suppressed mitochondrial function could have relatively high CHD7 levels, enabling these undifferentiated cells to retain differentiation potential. The level of CHD7 that can ensure the differentiation potential of cells varied across cell lines and culture methods, therefore we cannot determine a universal cutoff value for every cell line. However, H9 cells with a CHD7 copy number of less than 2000 copies/5ng total RNA showed a limited differentiation potential when cultured on VTN-Ncoated dishes (Figs. 1B, 2A, 3A).

In the previous sections, we have shown (1) the introduction of mCHD7 induced spontaneous differentiation (Fig.3A), (2) the differentiation process was coupled with the activation of mitochondrial function (Fig.2C), and (3) there was a reciprocal relationship between the CHD7 expression level and the degree of mitochondrial function in undifferentiated cells (Fig.2A). The question is how the CHD7 expression and the degree of mitochondrial function corelated each other. We showed culture medium selected a cell population to grow (Fig.1B), and the activation of mitochondria of cells in culture is directly affected by the formula of culture medium (Fig.2A). While, we could not demonstrate the relationship between formula of the medium and the expression of CHD7, rather the CHD7 expression level in cells as assessed by flow cytometry showed a broad coefficient of variation (CV) just after the culture medium was changed from RFF2 to Es8 (Fig.3B, P0). Then, the level of CHD7 expression came to converge at the highest level during the culture (Fig.3B, P5 and P7). This result suggests that cells with a higher CHD7 expression have a growth advantage and become dominant during the culture. This presumption was manifested by the CHD7 knockdown experiment using siCHD7. This experiment indicated that the level of CHD7 was positively correlated with cell proliferation potential (Fig.3C) and cells with a higher CHD7 expression became dominant due to a growth advantage after a couple of passages. This would explain the observation that the expression of CHD7 reached its highest level during the late passages, as shown in Fig.3B (P7).

In addition to the differentiation potential, the retention of self-renewal potential is a key feature of PSCs. PSCs require cell-to-cell contact to grow and, therefore, PSCs need to form colonies. For the clinical application of PSCs, we must focus on an animal-free cell culture system. Therefore, synthetic ECM was used as the dish-coating material based on regulatory considerations. However, cells on the rims of the 2-dimensional (2-D) colonies lack the signals triggered by cell-to-cell contact at one open end, which is in sharp contrast with the majority of cells located in the middle of the colony that are surrounded by other cells along their cell membrane without interruption. Cells along the rim of the colony have an uneven distribution of molecules and ion flux related to the cell-to-cell contact-mediated signals and undergo uneven segregation in mitosis. This, then, results in a break of the self-renewal state where two identical daughter cells are generated from a mother cell, triggering spontaneous differentiation10,11,12. Indeed, cells on the rims of the colonies were positively stained with anti-superoxide dismutase 2 (SOD2) antibodies (Fig.4A). SOD2 is an enzyme that belongs to the Fe/Mn superoxide dismutase family, which scavenges excess ROS generated as a result of mitochondrial activation. SOD2 gene expression in H9 cells in the culture showed that these cells committed ectoderm and mesoderm differentiation (Fig.4A). Consequently, the population of undifferentiated cells would decrease if the spontaneously differentiated cells were not properly removed from the culture. Notably, the percentage of SOD2-positive cells (4.9%) on day 5 of culture with Es8/L511 was reduced after cells were seeded in single-cell suspensions on VTN-N(0.9%), L521-(2.6%), or L511-(2.8%) coated dishes after 30h (Fig.4B). This suggests that the ability of cells to adhere to the ECM was reduced in differentiated cells compared with undifferentiated cells, and the cell-binding ability of L511 or L521 for differentiated cells was higher than that of VTN-N. Gene expression profiles showed that cells cultured on L511 or L521 were committed to ectoderm and mesoderm differentiation (Fig.4B). Thus, by exploiting the reduced cell adhesion properties of differentiated cells and the less potent cell-binding properties of VTN-N, differentiated cells could be effectively eliminated from the culture at a single-cell level by seeding cells in a single-cell suspension at each passage.

The removal of differentiated cells by seeding on a less adhesive material. (A) H9 cells cultured with Es8 on L511-coated dishes for 5days were stained with anti-SOD2 antibodies (upper left panel), and SOD2-positive (red dots) and SOD2-negative (black dots) cells were sorted (upper right panel) to examine the ectodermal or mesodermal gene expression patterns of each population by RT-qPCR (bottom panel). (B) H9 cells cultured with the conditions described in panel A (total 2.1106 cells, 4.9% SOD2-positive cells) were collected and 5.0104 cells from them were seeded as single-cell suspensions either on L511-, L521-, or VTN-Ncoated dishes and cultured for 30h with Es8. The total cell numbers harvested and the percentages of SOD2-positive cells under different culture conditions are shown. The ectodermal or mesodermal gene expression levels of cells cultured under relevant conditions as determined by RT-qPCR are shown in the lower bar graph. The interpretation of gene expression levels determined by RT-qPCR is shown in the attached table. Representative results from three independent experiments are shown.

In previous sections, we showed data using ESC H9 cells as the standard control PSC clone to avoid possible arguments about iPSC clones having diverse genetic and epigenetic backgrounds. Therefore, there is a strong need to standardize iPSC clones to develop iPSC-based cell therapy. In the previous section, we showed that the differentiation potential of even ESC H9 cells, which have relatively homogenous genetic and epigenetic profiles, could be altered by culture medium (Fig.1) and there is a possibility that we can improve the differentiation potential by optimizing culture conditions. Optimized culture conditions may include the selection of an appropriate culture medium that supports the glycolytic pathway, the seeding of cells as single-cell suspensions during passaging, and the culture of cells on an ECM substrate with a relatively weak cell-binding capacity, such as VTN-N, to minimize the inclusion of differentiated cells in undifferentiated cell cultures and to maintain the self-renewal population for the expansion of cell clones. To verify that culture conditions improved the differentiation potential of established iPSC clones, we cultured the iPSC clones 253G113, 201B75, PFX#9, and SHh#24 and the ESC clone H9 (control) with iPSC medium4 or mTeSR1 and maintained them on feeder cells or on L511- or L521-coated dishes that were transferred to Es8 medium, cultured on VTN-Ncoated dishes, and passaged as single-cell suspensions. The CHD7 expression profile by flow cytometry and the number of EBs formed before and after the transition to Es8/VTN-N culture were measured. Notably, increased levels of CHD7 expression by flow cytometry before and after recloning (Fig.5A) may be a good index for an improved differentiation potential of cells, as manifested by an increase in the number of EBs formed (Fig.5B). The convergence of CHD7 expression by flow cytometry (Fig.5A) may represent a decreased variance in the differentiation potential among iPSCs in a given culture.

Recloning of cells with differentiation potential based on culture conditions. (A) iPSC clones (201B7, PFX#9, SHh#2, or 253G1 cells) or ESC clones (H9 cells) were cultured either on feeder cells or on L511- or L521-coated dishes with iPSC or mTeSR1 medium. Clones were then transferred to Es8 medium and cultured on VTN-Ncoated dishes. The mean and convergence of CHD7 expression of cell clones was determined by flow cytometry before (gray histogram) and after (red histogram) changing culture conditions. Representative results from three independent experiments are shown. (B) Flow cytometric analysis of cell clones for the mean and coefficient of variation (CV) measured before (circle) and after (square) changing culture conditions are plotted on the left panel and the differentiation potential before and after changing the culture conditions was assessed by the number of EBs formed and is shown on the right panel. The data set shown in (B) was generated from the same samples shown in (A).

Although we cannot alter the genetic background of individual cells by changing culture conditions, a cell population with a higher differentiation potential could be selected to grow, or be recloned, by culture conditions that support the glycolytic pathway and by eliminating spontaneously differentiated cells by seeding on an ECM with a less potent cell-binding capability, thus exploiting their reduced adhesive properties. This could also reduce the variability in differentiation potential, especially among iPSC clones.

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Improving the differentiation potential of pluripotent stem cells by optimizing culture conditions | Scientific Reports - Nature.com

IPS Cell Therapy Comments Off on Improving the differentiation potential of pluripotent stem cells by optimizing culture conditions | Scientific Reports – Nature.com | August 26th, 2022

Jeanne Loring likes to say shes been to space without her feet even leaving the ground.

Just weeks ago, the Scripps Research Institute professor of molecular medicine sent some of her own genetically mapped cells to space as part of first-of-its-kind research to study the progression and onset of Parkinsons disease, multiple sclerosis and other neurodegenerative diseases.

I love traveling. Ive been on all the continents, and so I figured, whats left? Loring said jokingly. I just jumped at the opportunity when I learned that it was possible.

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In July, the cells arrived via cargo spacecraft at the International Space Station, where they remained under close observation for about a month 250 miles above Earth, and traveling at 17,500 miles per hour before they splashed back down to Earth last week.

The study is part of new National Stem Cell Foundation-funded neurodegeneration research to observe how cells communicate in microgravity in a way not possible on Earth, explained Paula Grisanti, founder and CEO of the foundation.

Its really pure exploration at this point, because theres no history of anybody doing this before, she said. Were paving the path.

An organoid derived from Dr. Jeanne Lorings induced pluripotent stem cells is prepared to be sent to the International Space Station.

(Courtesy of Dr. Davide Marotta)

Loring, a Del Mar resident who is one of the worlds leading experts in Parkinsons and a senior scientific advisor for the foundation, has been working with human-induced pluripotent stem cells since the technology was first discovered in 2006.

Called organoids, these cells are made from human skin tissue, which is put into a culture dish and turned into pluripotent stem cells, Loring explained.

Pluripotent stem cells only exist in culture dishes, they dont exist in our bodies, she said. Pluripotent means they can form any cell type in the body so for Loring, that meant forming nerve cells to create brain-like structures.

Its hard to study peoples brains, Loring said. You can do all this external stuff like they do with physical exams, but theres not any window into the brain so this is providing a sort of brain avatar.

Organoids provide a stand-in for the brain that can be studied by researchers, Loring explained. They make connections with each other, the cells talk to each other, so in a lot of ways, its a really good model of the brain, she added.

Moreover, the organoids mimic the brains of people with MS and Parkinsons.

Loring has been working with these organoids for years through Aspen Neuroscience, a San Diego-based company she co-founded that is working to create the worlds first personalized cell therapy for Parkinsons, using a patients own cells so they dont have to worry about rejection. Clinical trials may start as early as next year, she said.

Tubes containing neural organoids are loaded into a rack in preparation for placement in Cube Lab to travel to the International Space Station.

(Courtesy of Space Tango)

For the last four years, the foundations team of bicoastal researchers has been working together to study these organoids in space.

While an experiment in space presents its own challenges, Loring said its worth the work, as researchers hope to gain valuable and unique insight into how disorders like Parkinsons and MS develop. You can see them interacting and talking to each other in 3-D in a way that you cannot on Earth, Grisanti said.

Along with Lorings healthy organoids, which are used as a control, organoids derived from patients with Parkinsons and MS were sent to the space station, while the entire experiment was replicated on Earth.

Specifically, researchers are studying the neuroinflammation in the organoids, which is like when the immune system in the brain is overactive, Grisanti explained.

Organoid cultures are sealed in holders and ready to be placed in Cube Lab for space flight. The cover shows National Stem Cell Foundations SpaceX CRS-25 mission patch.

(Courtesy of Space Tango)

What we hope to find is a point at which things start to go wrong in those neurodegenerative diseases, where we could then intervene with a new drug or cell therapy, she said. And were seeing signs that that happens more in space than it does on the ground, so it helps create the type of interaction that you would see early in a neurodegenerative disease.

Grisanti said they hope to be able to use this research to develop a new drug or cell therapy to treat these disorders and potentially other neurodegenerative diseases in the future.

I think weve cracked the door open, but weve got some more flying to do, she added.

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To better understand Parkinson's disease, this San Diego expert sent her own cells to space - The San Diego Union-Tribune

Skin Stem Cells Comments Off on To better understand Parkinson’s disease, this San Diego expert sent her own cells to space – The San Diego Union-Tribune | August 26th, 2022

But there are other hurdlessome so challenging that many scientists have given up. For one thing, nudging the stem cells in the right direction requires, it seems, a unique touch and expertise. Not just anyone will be able to make egg and sperm cells in the lab, says Saitou.

Saitou and Hayashi, now at Kyushu University, lead world-renowned teams of extraordinary skill. Their achievements might not have been possible without the contributions of Hiroshi Ohta, for example. Ohta is an expert in anesthetizing newborn mice using ice, performing intricate surgery on them, and injecting cells into the animals miniature gonads. The entire procedure must be completed within five minutes or the animals die. Only a few people have such skills, which take months to develop. I think our group was kind of lucky, says Saitou. It was a get-together of many talented scientists.

The work is hampered by the lack of in-depth knowledge about how the primitive forms of egg and sperm cells develop naturally in the embryoa process that is far from fully worked out in humans. Some of the embryos cells begin to differentiate into these primitive sex cells at around 14 days. But in some countries, it is illegal for researchers to even grow human embryos beyond 14 days. They would send me to jail if I went beyond day 14, says Azim Surani, who is working with precursors to artificial sex cells at the University of Cambridge in the UK.

The problem, from a research point of view, is that the 14-day rule comes in just as the embryos start to get interesting, says Surani. Without being able to easily study the critical process of how primitive cells begin forming egg and sperm cells, scientists are limited in their ability to mimic it in the lab.

Even if scientists were able to study embryos more freely, some mysteries would remain. Once the cells that make eggs and sperm are created, they are held in a kind of suspended animation until puberty or ovulation. What happens to them in the years in between? And how important is this phase for the health of mature eggs and sperm? The honest answer is we dont know, says Surani.

The stem cells in the lab must also be generated and cared for under precise conditions. To survive, they must be bathed in a cocktail of nutrients that must be replaced every day. Its very time consuming and labor intensive and it takes a lot of money, says Bjorn Heindryckx at Ghent University in Belgium, one of the scientists who have given up on creating human eggs this way in the lab. The outcome was too limited for the effort and the money that we spent on it, he says.

Part of the challenge is that for the precursor stem cells to develop into fully matured egg or sperm cells, they must be placed in an environment mimicking that of newly developing ovaries or testes. Researchers studying mice use tissue taken from mouse embryos to induce the stem cells to differentiate into sex cells. But similarly using human tissue from discarded embryos is ethically and legally problematic. So scientists are working on ways to create the right environment without using tissue from embryos.

The upshot is that it will likely take a highly skilled team years of dedicated research. Its not impossible, but it would not be easy to do, says Surani.

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Inside the race to make human sex cells in the lab - MIT Technology Review

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Westford, USA, Aug. 25, 2022 (GLOBE NEWSWIRE) -- As the world increasingly becomes connected and people live longer, surgery and medical procedures become more complex. Surgery, one of the most common medical procedures, is now estimated to use over 1 million surgical tools each year. In order to meet the rising demand for surgical tools, surgeons are turning to biomaterials as a key component in their procedures. The main reason for this growth of the global biomaterials market is the increasing demand for novel biomaterials in various sectors such as automotive, aerospace, construction, and medical applications.

The growing demand for biomaterials has led to several companies developing unique biomaterials specifically for surgery. Some of the most well-known biomedical materials including polypropylene microspheres, chitosan hydrogel, and alginate matrix were pioneers in the field of biomaterials. Today, there are numerous new types of biomaterials being developed and marketed for a variety of medical applications, such as wound healing and orthopedic surgery. Global biomaterials market is expanding rapidly due to increasing public awareness of the benefits of using these materials and growing demand from pharmaceutical and medical device companies.

SkyQuest has published a report on global biomaterials market. The report provides a detailed market analysis, which would help the market participant in gaining is insights about market forecast, company profiles, market share, pricing analysis, competitive landscape, value chain analysis, porters five, and pestle among others.

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Demand For Biomaterials in the Healthcare Industry will Grow by 53% Over the Next Five Years

The demand for biomaterials market in the healthcare industry is growing rapidly, according to SkyQuest study. We studied global economic data and discovered that the demand for biomaterials in the healthcare industry will grow by 53% over the next five years. In 2021, 10.7 million patients used some kind of biomaterials across different applications such as wound care, tissue implant, surgeries, and medical devices, among others. This rising demand is impacting not only hospitals and clinics, but also diagnostic laboratories and pharmaceutical companies.

Most biomedical materials are manufactured from organic materials such as skin, bone, cartilage, and tendons. While these materials can be derived from a variety of sources, synthetic biomedical materials are often cheaper and more readily available. However, synthetic biomedical materials do not have the same properties as natural materials, which means they may not be as effective when used in medical treatments. Biologically based biomaterials are more effective because they can mimic the properties of natural tissues. Their potential benefits make them a highly desired commodity in the healthcare industry across the global biomaterials market. In 2021 alone, sales of artificial joints were worth $2.2 billion, while sales of regenerative medicine products such as stem cells and platelet-rich plasma were estimated to be worth $8.8 billion in the same year.

SkyQuest has done a detailed study on global biomaterials market and prepared a report that also covers current consumer base, potential demand for products, demand analysis by category and volume, expected growth, prominent growth factors, market dynamics, trends, opportunities, and innovation, among others.

Browse summary of the report and Complete Table of Contents (ToC):

https://skyquestt.com/report/biomaterials-market

Top 4 Biomaterials in Global Market

1. Stem cells- Stem cells have become one of the most promising areas of biomaterial research because they can be modified to create a wide variety of tissue types, including cartilage, skin, and bone.

2. Chitosan- Chitosan is a natural polymer found in creatures ranging from crabs to shrimp, and it is prized for its ability to form strong and durable bonds with other materials.

3. Polycaprolactone- Polycaprolactone is a modified form cellulose that has been shown to have many potential biomedical applications, including as a replacement for hard tissues like heart valves and bones.

4. Mesenchymal stem cells- Mesenchymal stem cells (MSCs) are adult cells found in the connective tissue and skeletal muscles of mammals. MSCs have characteristics that make them especially effective at repairing tissues damaged by disease or injury, which is why they are commonly used in studies on regenerative therapies.

Recent Advancements in Biomaterials Market

Successful applications of biomaterials in disease treatment have made them a preferred choice for many medical procedures. For example, use of biomaterials for artificial heart valves has revolutionized the way these devices are operated and prevented heart failure in patients.

In addition, various biomaterials are being developed for use in regenerative medicine. For example, researchers in the global biomaterials market are exploring the possibilities of using nano-sized polymers to promote the growth of new tissue in injured or damaged tissues. This approach may prove to be an effective way to restore function to damaged organs and limbs.

Biomaterials are also being used to create new types of prosthetic devices. For example, doctors are currently testing a new type of artificial hip that uses a biocompatible material as its main component.

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SkyQuests report on global biomaterials market would help you in gaining insights about current developments and its impact on the overall market growth, pricing, demand and supply, change in growth strategies of existing players, among others. Also, the report would help in understanding how the market value is changing and affecting the forecast revenue over the period.

Top Players in the Global Biomaterials Market

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Global Cell Therapy Market

Global Flow Cytometry Market

Global Bioinformatics Market

Global Synthetic Biology Market

Global Biopharmaceutical Analytical Testing Services Market

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Global Biomaterials Market to Reach Value of $372.7 Billion by 2028 | Demand For Biomaterials in the Healthcare Industry will Grow by 53% Over the...

Skin Stem Cells Comments Off on Global Biomaterials Market to Reach Value of $372.7 Billion by 2028 | Demand For Biomaterials in the Healthcare Industry will Grow by 53% Over the… | August 26th, 2022

We are what we eat. And drink. And how we sleep, detox, and exercise or not.

Nothing new there. But in a world where new-to-market serums, creams, and spiritual berry tonics extracted by hand by Tibetan monks are in our (digital) face every day, were being presented with so many cool options on how to cleanse, moisturize, and treat wrinkles, lackluster skin, and hair that its next to impossible to keep up, let alone care for.

And while I wont be ditching my tried-and-true products any time soon, these newer, technologically advanced plant-based offerings are, in truth, quite effective. Products flooded with adaptogens help the body respond and adapt to various kinds of stress and inflammation. And how we weave them into our lifestyle regimens can be fun too.

Rather than barrage you with a ton of products, I thought a conversation regarding upcoming trends that embrace these new, full-circle, inside-and-out additions to our anti-aging routines is in order. We may have to look a little harder for these over-the-counter retail items, but not for long. Keep in mind that several of these brands combine two or three categories as ingestibles and topicals, which include CBD, functional mushrooms, and waterless skin care all of it nonpsychoactive, of course.

While recreational and medicinal marijuana are slowly becoming legal in more and more states, its tempting to get into the weeds with a cannabis/hemp/CBD tutorial. Lets simplify: it all comes from the same hemp plant thats loaded with restorative and preventative properties. CBD is legal (no high) and widely used for general to advanced wellness. Categories include singular isolates (113+ CBD extracts); broad spectrum (whole plant extract minus THC); and full spectrum (whole plant extract with less than 0.3 percent THC, the legal limit for all CBD products in the U.S.).

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A Groovy Guide to Anti-Aging Products With CBD and Mushrooms - Out Magazine

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Figure 3. HSCs and restricted haematopoietic progenitors occupy distinct niches in the bone marrow

a. HSCs are found mainly adjacent to sinusoids throughout the bone marrow,,,, where endothelial cells and mesenchymal stromal cells promote HSC maintenance by producing SCF, CXCL12,,, and likely other factors. Similar cells may also promote HSC maintenance around other types of blood vessels, such as arterioles. The mesenchymal stromal cells can be identified based on their expression of Lepr-Cre, Prx1-Cre, Cxcl12-GFP, or Nestin-GFP transgene in mice and similar cells are likely to be identified by CD146 expression in humans. These perivascular stromal cells, which likely include Cxcl12-abundant Reticular (CAR) cells, are fated to form bone in vivo, express Mx-1-Cre and overlap with CD45/Ter119PDGFR +Sca-1+ stromal cells that are highly enriched for MSCs in culture. b. It is likely that other cells also contribute to this niche, likely including cells near bone surfaces in trabecular rich areas. Other cell types that regulate HSC niches include sympathetic nerves,, non-myelinating Schwann cells (which are also Nestin+), macrophages, osteoclasts, extracellular matrix ,, and calcium. Osteoblasts do not directly promote HSC maintenance but do promote the maintenance and perhaps the differentiation of certain lymphoid progenitors by secreting Cxcl12 and likely other factors,,,. Early lineage committed progenitors thus reside in an endosteal niche that is spatially and cellularly distinct from HSCs.

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The bone marrow niche for haematopoietic stem cells - PubMed

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What Is a Bone Marrow Transplant?

A bone marrow transplant is a medical procedure performed to replace bone marrow that has been damaged or destroyed by disease, infection, or chemotherapy. This procedure involves transplanting blood stem cells, which travel to the bone marrow where they produce new blood cells and promote growth of new marrow.

Bone marrow is the spongy, fatty tissue inside your bones. It creates the following parts of the blood:

Bone marrow also contains immature blood-forming stem cells known as hematopoietic stem cells, or HSCs. Most cells are already differentiated and can only make copies of themselves. However, these stem cells are unspecialized, meaning they have the potential to multiply through cell division and either remain stem cells or differentiate and mature into many different kinds of blood cells. The HSC found in the bone marrow will make new blood cells throughout your lifespan.

A bone marrow transplant replaces your damaged stem cells with healthy cells. This helps your body make enough white blood cells, platelets, or red blood cells to avoid infections, bleeding disorders, or anemia.

Healthy stem cells can come from a donor, or they can come from your own body. In such cases, stem cells can be harvested, or grown, before you start chemotherapy or radiation treatment. Those healthy cells are then stored and used in transplantation.

Bone marrow transplants are performed when a persons marrow isnt healthy enough to function properly. This could be due to chronic infections, disease, or cancer treatments. Some reasons for a bone marrow transplant include:

A bone marrow transplant is considered a major medical procedure and increases your risk of experiencing:

The above symptoms are typically short-lived, but a bone marrow transplant can cause complications. Your chances of developing these complications depend on several factors, including:

Complications can be mild or very serious, and they can include:

Talk to your doctor about any concerns you may have. They can help you weigh the risks and complications against the potential benefits of this procedure.

There are two major types of bone marrow transplants. The type used will depend on the reason you need a transplant.

Autologous transplants involve the use of a persons own stem cells. They typically involve harvesting your cells before beginning a damaging therapy to cells like chemotherapy or radiation. After the treatment is done, your own cells are returned to your body.

This type of transplant isnt always available. It can only be used if you have a healthy bone marrow. However, it reduces the risk of some serious complications, including GVHD.

Allogeneic transplants involve the use of cells from a donor. The donor must be a close genetic match. Often, a compatible relative is the best choice, but genetic matches can also be found from a donor registry.

Allogeneic transplants are necessary if you have a condition that has damaged your bone marrow cells. However, they have a higher risk of certain complications, such as GVHD. Youll also probably need to be put onmedications to suppress your immune system so that your body doesnt attack the new cells. This can leave you susceptible to illness.

The success of an allogeneic transplant depends on how closely the donor cells match your own.

Prior to your transplant, youll undergo several tests to discover what type of bone marrow cells you need.

You may also undergo radiation or chemotherapy to kill off all cancer cells or marrow cells before you get the new stem cells.

Bone marrow transplants take up to a week. Therefore, you must make arrangements before your first transplant session. These can include:

During treatments, your immune system will be compromised, affecting its ability to fight infections. Therefore, youll stay in a special section of the hospital thats reserved for people receiving bone marrow transplants. This reduces your risk of being exposed to anything that could cause an infection.

Dont hesitate to bring a list of questions to ask your doctor. You can write down the answers or bring a friend to listen and take notes. Its important that you feel comfortable and confident before the procedure and that all of your questions are answered thoroughly.

Some hospitals have counselors available to talk with patients. The transplant process can be emotionally taxing. Talking to a professional can help you through this process.

When your doctor thinks youre ready, youll have the transplant. The procedure is similar to a blood transfusion.

If youre having an allogeneic transplant, bone marrow cells will be harvested from your donor a day or two before your procedure. If your own cells are being used, theyll be retrieved from the stem cell bank.

Cells are collected in two ways.

During a bone marrow harvest, cells are collected from both hipbones through a needle. Youre under anesthesia for this procedure, meaning youll be asleep and free of any pain.

During leukapheresis, a donor is given five shots to help the stem cells move from the bone marrow and into the bloodstream. Blood is then drawn through an intravenous (IV) line, and a machine separates out the white blood cells that contain stem cells.

A needle called a central venous catheter, or a port, will be installed on the upper right portion of your chest. This allows the fluid containing the new stem cells to flow directly into your heart. The stem cells then disperse throughout your body. They flow through your blood and into the bone marrow. Theyll become established there and begin to grow.

The port is left in place because the bone marrow transplant is done over several sessions for a few days. Multiple sessions give the new stem cells the best chance to integrate themselves into your body. That process is known as engraftment.

Through this port, youll also receive blood transfusions, liquids, and possibly nutrients. You may need medications to fight off infections and help the new marrow grow. This depends on how well you handle the treatments.

During this time, youll be closely monitored for any complications.

The success of a bone marrow transplant is primarily dependent on how closely the donor and recipient genetically match. Sometimes, it can be very difficult to find a good match among unrelated donors.

The state of your engraftment will be regularly monitored. Its generally complete between 10 and 28 days after the initial transplant. The first sign of engraftment is a rising white blood cell count. This shows that the transplant is starting to make new blood cells.

Typical recovery time for a bone marrow transplant is about three months. However, it may take up to a year for you to recover fully. Recovery depends on numerous factors, including:

Theres a possibility that some of the symptoms you experience after the transplant will remain with you for the rest of your life.

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Bone Marrow Transplant: Types, Procedure & Risks - Healthline

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Cord blood banking can treat a wide range of illnesses. This type of blood contains high concentrations of special stem cells. The stem cells collected from the umbilical cord can assist with autoimmune disorders and other diseases. The process of cord blood banking often occurs when a medical professional such as an obstetrician-gynecologist takes blood from an umbilical cord after the birth of a baby. The cord blood is then collected and processed. Cord blood banking has the potential to save lives.

Collected cord blood treats many diseases. The diseases that cord blood is known to combat range from leukemia to sickle cell anemia. The cord blood often helps improve an individuals immune system and bone marrow. The blood thats found within the umbilical cord is considered special because it treats a wide range of illnesses. Although it tends to work best for the child and mother, the blood can also assist other people if the results from testing for matches prove beneficial. Collecting cord blood remains an excellent option for parents and people with histories of certain illnesses. Cord blood collection is recommended for people interested in taking a proactive approach to potential future illnesses. As the saying goes, health is wealth.

Collecting cord blood and cord tissue is important because the stem cells they contain can transform into other human cells. Stem cells offer flexibility and adaptability that can prove useful when treating certain cancers.

The stem cells collected from cord blood offer almost 10 times the number of stem cells that can be collected using alternative types of collection. The process of collecting stem cells from a clamped umbilical cord after birth is considered an easier process than collecting stem cells from bone marrow.

Stem cells collected from cord blood are viewed as more favorable than those collected from bone marrow because the stem cells from cord blood have a lower likelihood of passing on blood-borne illnesses.

Cord blood remains a scarce resource for both research and stem cell transplants because of a low and limited supply. The amount of cord blood that can be collected remains relatively low because only so much can be collected after birth.

The blood is drawn from a clamped umbilical cord after birth and placed into a sterile bag. Cord blood is tested before it is accepted by a cord blood bank. Not every unit of cord blood meets the specified criteria. For example, some units of cord blood are not deemed worth the resources to cryogenically save because they lack stem cells. The cord blood is examined to make sure that it is not contaminated and does not contain any potential diseases. Blood is also tested to know if it has a high-enough level of blood-forming cells. Such inspections help create safeguards for people interested in obtaining cord blood for treatment. Cord blood that does not meet the strict standards for transplant use can be used for research.

The process of collecting cord blood for public cord blood banks is often not possible with twins because they are often born much smaller than other babies in addition to often having less cord blood. Public banks typically do not allow collections from twin births. In contrast, private banks will store cord blood from twins for possible use by the family.

Private cord blood banks are an excellent option in case one of your children becomes sick. If one of your children becomes ill, then having saved their cord blood or cord tissue can boost their immune system or improve bone marrow. Having a childs previously saved cord blood from their umbilical cord improves the likelihood of a successful transplant. The blood fights certain cancers as well as specific blood disorders.

An additional benefit of cord blood banking is that other siblings and close family members can use the blood. Using the stem cells from a sibling can prove useful if one of your children develops a genetic disorder. For example, a person with a genetic disorder such as cystic fibrosis cannot be treated by their own cord blood. Cord blood collected from the siblings of that person can often be used to combat the disorder.

A public cord blood bank follows government regulations to protect the public from harm by maintaining certain set standards. The banks follow a wide range of regulations such as state laws and regulations in combination with U.S. Food and Drug Administration (FDA) regulations. If a collected unit or sample of cord blood does not meet the set standards, it is usually used for research or discarded.

Public cord blood banks allow individuals to obtain cord blood for uses such as stem cell transplants. Cord blood units collected and provided to a public cord blood bank are usually placed on a registry to more easily be matched with patients in need.

Cord blood is stored in a public or private cord blood bank with cryogenic preservation.

Some cord blood banks offer the option to preserve both cord blood and cord tissue to collect different types of cells. If possible, saving both the cord blood and cord tissue can help collect more cells for future use.

Private cord blood banks allow direct family members and approved individuals to access personally stored cord blood. In contrast, public cord blood banks collect donations of blood usually at no cost to the donor. The collections at a public bank are then accessible to members of the public on an as-needed basis for allogeneic transplants.

Private cord blood banks: Private cord blood banks allow people to save their childs cord blood and cord tissue for the future. They can be expensive for the initial setup, and they charge annual fees for cord blood storage. However, the benefits can outweigh the costs for parents with other children who have known illnesses that can be treated using cord blood. This type of banking ensures that a family maintains possession of their cord blood so that it can be used as needed by members of the specific family. The U.S. has over 25 private cord blood banks that families can use. If a family elects to use a private cord bank, then a medical carrier service will retrieve the cord blood from the hospital and transport it to the cord blood bank. The courier service assists in making transport more accessible to a wider range of families and eases the burden felt by new parents by checking off one activity from a new parents busy to-do list.

Public cord blood banks: Cord blood donations to public banks are frequently used for research. The banks also help people to obtain access to cord blood for transplants. Individuals donate their babys cord blood without charge, which provides other people the ability to receive much-needed treatment. Public cord banks located throughout North America allow more people to access these services.

Hybrid cord blood banks: Some banks offer public and private services. These banks store your childs blood for the future and accept cord blood donations for use by the public. Hybrid cord blood banks help people to access cord blood from various areas within the country as well as from the larger international cord blood banking system. Hybrid banks provide improved access to a wider range of available cord blood.

An autologous transplant or stem-cell transplant occurs when healthy stem cells from your body are used to help improve your bone marrow. Bone marrow can be found within your bones, and it helps to create red and white blood cells. An individual with weakened bone marrow faces life-threatening complications. An autologous transplant helps to address these concerns by placing previously removed stem cells back into your body.

The process is common for individuals that need cancer treatment such as chemotherapy. People who need chemotherapy will have some healthy stem cells removed and then undergo chemotherapy. Afterward, the healthy stem cells are replaced to help improve their bone marrow.

An autologous transplant shouldnt be confused with an allogeneic stem cell transplant. The main difference is that an allogeneic stem cell transplant comes from other people while an autologous stem cell transplant comes from yourself.

When researching cord blood banking, its common to have questions along the way. If you intend to give birth, consider the benefits of cord blood banking while speaking with the hospital and cord blood bank to understand the expected process. Ask about possible risks and prices before making a final decision.

Private cord blood banking can be expensive. One reason that cord blood banking has high costs is that its not usually covered by insurance. However, families with histories of certain illnesses have the possibility of getting a portion of the costs offset by insurance. Costs usually include initial storage fees, which are $1,000 or more, in addition to yearly storage fees. The storage fees range between $200 and $300 annually.

Not all hospitals offer cord blood banking procedures. The hospitals that do offer cord blood banking usually do not complete the banking procedure in-house. The hospitals and cord blood banks often work in tandem because the hospitals extract the cord blood from the umbilical cord while cord blood banks store the cord blood. See if the hospital youll be using provides the option of a cord blood procedure. Its common for a courier to transport the cord blood to a specified cord blood banking lab to complete the procedure.

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What is Cord Blood Banking? - Benzinga

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What Are Hematopoietic Stem Cells and Why Are They Important? Hematopietic stem cells (HSCs) are multipotent cells found in the blood and bone marrow with the ability to self-renew and differentiate into multiple cell types during bone marrow hematopoiesis. Clinicians use HSCs to replace or repopulate a patients blood as a form of regenerative medicine. Research into HSC development and aging facilitates better in vitro HSC expansion and broadens their potential for disease treatment, enhancing their clinical therapeutic effects.

How Hematopoietic Stem Cells DevelopHSCs begin their development during embryogenesis in the dorsal aortic tissue and are additionally found in the placenta, yolk sac, and fetal liver. This fetal hematopoiesis process is necessary to produce the blood cells required for tissue development while generating a pool of undifferentiated HSCs. At birth, these HSCs migrate into and populate the newly-formed bone marrow and maintain a steady state of self-renewal and differentiation.1 HSCs function by producing red blood cells, platelets, and white blood cells throughout life, maintaining their levels following bleeding and infection. HSCs generally give rise to partly differentiated but proliferative progenitors, which differentiate into mature cells. Because of this process, true HSCs are relatively rare in the human body.2

Using Hematopoietic Stem Cells for Research and TreatmentHematopoietic stem cell transplantsFor more than 60 years, hematopoietic stem cell transplants (HSCTs) have been the most common form of HSC therapy, and are a standard option for treating hematologic malignancies, immunodeficiency, and defective hematopoiesis disorders. HSCs are now derived from multiple sources, such as peripheral and cord blood and bone marrow. Before transplantation, the receiving patient must undergo severe immunosuppressive procedures to prevent rejection of the new stem cells.3

Hematopoietic stem cell isolationThe most common HSC isolation method involves removing blood cells from plasma using density gradient centrifugation followed by magnetic bead isolation using the CD34+ surface marker, a general marker for all hematopoietic progenitors. Using flow cytometry, scientists sort specific HSC cell types based on common cell surface markers.4 Clinicians then intravenously infuse these cells into the receiver patients marrow where they engraft and repopulate the blood and immune system. In blood cancers such as leukemias and lymphomas, restoration of the blood system by HSCT allows patients to receive high-dose chemotherapy treatments, ridding them of malignant cells. In patients with red blood cell conditions where continuous blood transfusions are not an option, such as thalassemia major, HSCT results in 80 percent disease-free survival.5

Hematopoietic stem cells in gene and tissue regeneration therapyBone marrow hematopoietic stem cells also differentiate into cells of other lineages, such as endothelial cells, cardiomyocytes, neural cells, and hepatocytes, in a process called transdifferentiation. Because adult stem cells are rare, understanding the mechanisms behind HSC transdifferentiation could provide an additional source of tissue-specific multipotent cells and influence future clinical methods for tissue regeneration. HSCs can also help repair injured organs by releasing regenerative cytokines and recruiting cells to the damage site.5 Some of the latest advances in HSC therapeutic research involve using methods such as CRISPR for correcting genetically-defective HSCs. These methods will allow a patient to receive their own genetically-compatible (syngeneic) HSCs. These are called allogeneic transplants and are more effective at avoiding graft-versus-host disease, a condition where transplants from a donor are rejected by the recipients body, leading to an immune response against other tissues and organs. Creating genetically-corrected induced pluripotent stem cells (iPSCs) from patient skin tissues and differentiating them into HSCs has also been an active area of research, although current methods remain costly and time-consuming.6 Further research is necessary to take advantage of these remarkable multipotent cells in disease therapies.

References

1. H.K. Mikkola, S.H. Orkin, The journey of developing hematopoietic stem cells, Development, 133(19):3733-44, 2006.

2. G.M. Crane et al., Adult haematopoietic stem cell niches, Nat Rev Immunol, 17(9):573-90, 2017.

3. S. Giralt, M.R. Bishop, Principles and overview of allogeneic hematopoietic stem cell transplantation, Cancer Treat Res, 144:1-21, 2009.

4. B. Kumar, S.S. Madabushi, Identification and isolation of mice and human hematopoietic stem cells, Methods Mol Biol, 1842:55-68, 2018.

5. J.Y. Lee, S.H. Hong, Hematopoietic stem cells and their roles in tissue regeneration, Int J Stem Cells, 13(1):1-12, 2020.

6. S. Demirci et al., Hematopoietic stem cells from pluripotent stem cells: Clinical potential, challenges, and future perspectives, Stem Cells Transl Med, 9(12):1549-57, 2020.

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Brush Up: Hematopoietic Stem Cells and Their Role in Development and Disease Therapy - The Scientist

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According to the National Cancer Institute, over 60,000 people will be diagnosed with leukemia this year and 24.000 will die. The NCI explains, "There is no standard staging system for leukemia. The disease is described as untreated, in remission, or recurrent," and while there's no way to prevent the cancer, there are lifestyle choices like not smoking that help reduce the risk. Read on to learn what experts say about leukemia and to ensure your health and the health of others, don't miss these Sure Signs You've Already Had COVID.

The Mayo Clinic says, "Leukemia is cancer of the body's blood-forming tissues, including the bone marrow and the lymphatic system. Many types of leukemia exist. Some forms of leukemia are more common in children. Other forms of leukemia occur mostly in adults. Leukemia usually involves the white blood cells. Your white blood cells are potent infection fighters they normally grow and divide in an orderly way, as your body needs them. But in people with leukemia, the bone marrow produces an excessive amount of abnormal white blood cells, which don't function properly."

The National Cancer Institute says, "Leukemia is cancer that starts in the tissue that forms blood. Most blood cells develop from cells in the bone marrow called stem cells. In a person with leukemia, the bone marrow makes abnormal white blood cells. The abnormal cells are leukemia cells. Unlike normal blood cells, leukemia cells don't die when they should. They may crowd out normal white blood cells, red blood cells, and platelets. This makes it hard for normal blood cells to do their work. The four main types of leukemia are:6254a4d1642c605c54bf1cab17d50f1e

Acute lymphoblastic leukemia (ALL)

Acute myelogenous leukemia (AML)

Chronic lymphocytic leukemia (CLL)

Chronic myelogenous leukemia (CML)"

The Cleveland Clinic explains, "Leukemia is often considered a childhood illness. Even though it is one of the most common childhood cancers, the blood disorder cancer actually affects far more adults. According to the National Cancer Institute, leukemia is most frequently diagnosed among people between the ages of 65 and 74 years. The median age at diagnosis is 66. There are treatment options for patients of all ages, include chemotherapy and blood transfusions."

According to the Mayo Clinic, "Leukemia symptoms vary, depending on the type of leukemia. Common leukemia signs and symptoms include:

The Mayo Clinic states, "Factors that may increase your risk of developing some types of leukemia include:

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Sure Signs You Have Leukemia, Say Physicians Eat This Not That - Eat This, Not That

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MONDAY, Aug. 22, 2022 (HealthDay News) -- The U.S. Food and Drug Administration has approved Zynteglo (betibeglogene autotemcel), the first cell-based gene therapy for the treatment of adult and pediatric patients with beta-thalassemia who require regular red blood cell transfusions.

Zynteglo is a one-time, single-dose gene therapy product. Each dose of Zynteglo is customized and created using the patient's own bone marrow stem cells, which are genetically modified to produce functional beta-globin. The application was granted a rare pediatric disease voucher, as well as priority review, fast-track, breakthrough therapy, and orphan designations.

The approval was based on two multicenter clinical studies. Of 41 patients receiving Zynteglo, 89 percent achieved transfusion independence, defined as maintaining a predetermined level of hemoglobin without needing any red blood cell transfusions for at least 12 months. The most common adverse reactions seen with Zynteglo included reduced platelet and other blood cell levels, mucositis, febrile neutropenia, vomiting, fever, alopecia, nosebleed, abdominal pain, musculoskeletal pain, cough, headache, diarrhea, rash, constipation, nausea, decreased appetite, pigmentation disorder, and itch.

Given the potential risk for blood cancer associated with this treatment, patients receiving Zynteglo should have their blood monitored for at least 15 years for evidence of cancer. The FDA says patients should also be monitored for hypersensitivity reactions during Zynteglo administration and for thrombocytopenia and bleeding.

Approval of Zynteglo was granted to bluebird bio.

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FDA Approves First Cell-Based Gene Therapy for Beta-Thalassemia - HealthDay News

Bone Marrow Stem Cells Comments Off on FDA Approves First Cell-Based Gene Therapy for Beta-Thalassemia – HealthDay News | August 26th, 2022

Clogging a proteins active site is a straightforward way to take it offline. Thats why the active site is often the first place drug designers look when designing new drugs, Reich explained. However, about eight years ago he decided to investigate compounds that could bind to other sites in an effort to avoid off-target effects.

As the group was investigating DNMT3A, they noticed something peculiar. While most of these epigenetic-related enzymes work on their own, DNMT3A always formed complexes, either with itself or with partner proteins. These complexes can involve more than 60 different partners, and interestingly, they act as homing devices to direct DNMT3A to control particular genes.

Early work in the Reich lab, led by former graduate student Celeste Holz-Schietinger, showed that disrupting the complex through mutations did not interfere with its ability to add chemical markers to the DNA. However, the DNMT3A behaved differently when it was on its own or in a simple pair; it wasnt to stay on the DNA and mark one site after another, which is essential for its normal cellular function.

Around the same time, the New England Journal of Medicine ran a deep dive into the mutations present in leukemia patients. The authors of that study discovered that the most frequent mutations in acute myeloid leukemia patients are in theDNMT3Agene. Surprisingly, Holz-Schietinger had studied the exact same mutations. The team now had a direct link between DNMT3A and the epigenetic changes leading to acute myeloid leukemia.

Reich and his group became interested in identifying drugs that could interfere with the formation of DNMT3A complexes that occur in cancer cells. They obtained a chemical library containing 1,500 previously studied drugs and identified two that disrupt DNMT3A interactions with partner proteins (protein-protein inhibitors, or PPIs).

Whats more, these two drugs do not bind to the proteins active site, so they dont affect the DNMT1 at work in all of the bodys other cells. This selectivity is exactly what I was hoping to discover with the students on this project, Reich said.

These drugs are more than merely a potential breakthrough in leukemia treatment. They are a completely new class of drugs: protein-protein inhibitors that target a part of the enzyme away from its active site. An allosteric PPI has never been done before, at least not for an epigenetic drug target, Reich said. It really put a smile on my face when we got the result.

This achievement is no mean feat. Developing small molecules that disrupt protein-protein interactions has proven challenging, noted lead authorJonathan Sandovalof UC San Francisco, a former doctoral student in Reichs lab. These are the first reported inhibitors of DNMT3A that disrupt protein-protein interactions.

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A new kind of chemo - University of California

Bone Marrow Stem Cells Comments Off on A new kind of chemo – University of California | August 26th, 2022

When World Series champion Matt Szczur joined a bone marrow registry in 2007 as a freshman in college, he didnt think much of it. At the time, Szczur (pronounced like Caesar) was playing football for Villanova University. His coach, the legendary Andy Talley, encouraged him to get involved with an organization called Be The Match. As its name implies, the group matches bone marrow donors with recipients and raises money to help those suffering from life-threatening blood cancers, like leukemia and lymphoma, to provide necessary treatment.

I thought Id test [to be a match], and if I get a call, great, Szczur said in an interview with nft now. If not, it is what it is.

Fifteen years ago, the chances of matching a donor to a recipient were not what they are today. Bone marrow and cord blood unit donor-recipient pairing relies on matching human leukocyte antigen (HLA) types, something a patients ethnic background plays a prominent role in predicting. The more people in the registry, the larger the chances are of finding matches for people in need.

Szczur put it out of his mind until the fall of 2009 when he got a call from the Be The Match registry telling him they had found a recipient for his bone marrow type. It was right in the middle of playoffs, Szczur continued. I went and spoke with Talley, and he put his head down and said, Matt, I know youre going to do the right thing.

That match was a young girl named Anastasia Volkovskaya from Ukraine, whose doctors diagnosed her with leukemia just three months after being born.Doctors told us that she needs a transplant, explained Volkovskayas father Ivan in an ESPN video on Szczurs journey to becoming a donor produced for the sports-magazine broadcast series E:60. But in Ukraine, they dont do this. They said, Deal with it.

Volkovskayas parents kept searching for ways to save their daughter, eventually finding a clinic in Israel that could provide the transplant if they could find a matching donor. They found one in Szczur who was a 100 percent match. On May 4, 2010, Szczur donated his bone marrow in a peripheral blood stem cell (PBSC) procedure, a non-surgical operation in which doctors separate a patients blood-forming cells from the rest of the blood for bone marrow transplants.

It would take a while before Szczur learned precisely to whom he had donated. Confidentiality practices keep donors from learning the identity of recipients they match with for at least a year after the procedure. It deeply moved him when he finally learned Anatasias identity and got in contact with her and her family.

I remember like it was yesterday when I got the email from Be The Match about who she was and where shes from, Szczur said. When I was finally able to get in contact with her it was very emotional. I now have a son whos three. I understood the importance of [donating] then, but now, you know, Id do anything in the world to help my son, and Im sure thats how [ Volkovskayas parents] felt.

Volkovskayas parents appreciation for what Szczur did knows no bounds. This man gave life not just to one kid, he gave life to a whole family, said Anatasias mother Marina in ESPNs E:60 video.

Throughout his life, Szczur has engaged with art in one way or another. Whether sitting next to his father as a child and watching him make colorful bucktails (anglers lures traditionally made from deer hair) or experimenting with painting as a way to decompress from the stresses of being an athlete, its a part of life from which he never liked to stray very far.

After going on to play for Major League Baseball and winning the World Series with the Chicago Cubs in 2016, Szczur and his wife Natalie started a non-profit foundation dedicated to philanthropy and charity. To raise awareness for the foundation, Szczur decided to paint two self-portraits and auction them at an event the couple held in his hometown of Cape May, New Jersey. Both sold for $500. Cubs management later reached out to commission Szczur to make a painting of the teams World Series win, which the organization sold for $40,000.

Szczurs interest and involvement in NFTs would follow soon after. During the pandemic in 2020, fellow MLB player Micah Johnson reached out to Szczur to ask if he wanted to collaborate on an NFT project.I had read about the blockchain, but I had no idea what it was, Szczur said. I knew a little bit about Bitcoin, but Id never heard of Ethereum. I trusted Micah because he was a baseball player, and I knew he was a grinder. I respected him.

It doesnt get more real than someone who actually donated and saved the life of another human being.

Johnson suggested creating a portrait of George Floyd, and the two split the portrait in half, each depicting their side of Floyd in their own style. The limited edition piece sold out on Nifty Gateway in under six minutes, and the two used the funds raised from the painting to donate to initiatives dedicated to fighting injustices in the Black community.

Szczur has continued to expand into the world of crypto art, creating pieces that collectors can buy on OpenSea, Nifty Gateway, and SuperRare. His artwork frequently features bones and skeletons, which reflects the awareness hes trying to raise about bone marrow donations.

Having long wanted to work with Be The Match, Szczur found a golden opportunity to do so when a friend who had contacts at the bone marrow registry asked if he wanted to collaborate with the organization earlier this year.

Szczur and Be The Match are releasing two separate NFTs on Nifty Gateway in the coming days and weeks to raise awareness and money for the registry. The first is an open edition piece called Be The Match that drops on Friday, August 26, and will be available for sale for 48 hours. Editions start at $150 each. A second, limited-edition NFT drop will also be available through a 48-hour auction on Thursday, September 8, which Szczur says will be a different take on his previous skeleton and bone-themed NFT creations.

Half of all the proceeds from the NFT sales will go toward the Be The Match Foundation to help patients looking for a donor and add more potential donors to their registry.

This is Be The Matchs first experience in the NFT space, explained Alex Mensing, a Be The Match spokesperson in an interview with nft now. A partnership with Matt was a no-brainer. Hes been spreading awareness about bone marrow donations through his NFTs already, its something hes super passionate about. It doesnt get more real than someone who actually donated and saved the life of another human being. Thats our mission.

One of the reasons both Mensing and Szczur are excited to use NFTs as a way to spread awareness of the registry is because HLA types largely determine who can and cant match. The more diverse the registry, the greater the chances of those matches actually occurring.

I can say in all honesty that NFTs changed my life.

Right now, you see a disparity in the registry based on the ethnic diversity of the patient who is searching, elaborated Mensing. So today, a patient whos white or Caucasian has a 79 percent chance of finding a match on our registry. But Black or African American patient has only a 29 percent chance of finding a match. And so were doing a lot of recruitment to get more people to join the registry. And we have the most diverse registry in the world. Its just still not diverse enough to meet all of the patient need that exists.

Szczurs excitement for and dedication to the cause hes devoted the last decade to are admirable. Despite the maligned reputation people often attribute to NFTs and cryptocurrencies, hes adamant about their ability to do good in the world.

I can say in all honesty that NFTs changed my life, Szczur said. From top to bottom. I had no idea what I was going to do when I finished [playing] baseball. So, the transition from baseball to real life was helped so much by NFTs. I know people are skeptical about it, and they have the right to be. Cryptocurrency is so volatile. But they changed my life. Im grateful for the space.

The former MLB world champion is even more grateful for the chance to use the technology to spread awareness about a cause in which he firmly believes. His experience as a Be The Match donor is something he says will stick with him his entire life.

Theyre literally saving lives, Szczur emphasized. Everybody says theres no cure for cancer, but here we are doing this, and nobody really hears about it. So, I continue to push for this cure and for bone marrow awareness. I will continue to push this because I saw the impact that it had on my life and the impact it had on this familys life.

Those looking to support the foundations efforts and help save lives can add their names to Be The Matchs bone marrow registry here.

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A World Baseball Champion Is Using NFTs to Help Save Lives - nft now

Bone Marrow Stem Cells Comments Off on A World Baseball Champion Is Using NFTs to Help Save Lives – nft now | August 26th, 2022

Doctor with a cancer patient.

But, in order to defeat an enemy like cancer, you must first know more about it. Let's take a closer look at this dreadful disease.

Knowing the potential indicators of cancer is important regardless of your age or state of health. Symptoms are generally insufficient to diagnose the illness on their own. However, they may serve as hints for you and your physician to quickly identify and address the issue. Treatment for many types of cancer is most effective early on, when a tumor is tiny and the disease hasn't spread to other parts of the body.

The signs listed below are not exhaustive and do not necessarily indicate the presence of cancer. There are many common conditions that might share these symptoms. Visit your doctor as soon as possible so they can examine you more closely and take appropriate measures.

Cancer frequently exhibits the following symptoms in both men and women:

Artist's impression of cancer.

For men only, there are some sex-specific symptoms that could indicate the presence of cancer. For men, prostate, lung, and colorectal cancers are the most prevalent cancers that tend to develop.

Male cancer symptoms include:

Women, on the other hand, are more susceptible to some forms of cancer that are usually not expressed in males. Breast, lung, and colorectal cancer are some of the most common cancers in women, although men can also have these types of cancer. Cancers such as uterine, endometrial, cervical, vaginal, and vulvar cancers are particular to women.

Some of the warning signs for women include:

Every cancer starts in cells. More than a hundred billion billion (100,000,000,000,000) cells make up our bodies. Changes in one cell or a small number of cell can lead to the development of cancer.

Artistic impression of cancer cells.

When cells grow old or become damaged, they die, and new cells take their place. How much and how frequently cells divide is regulated by a number of factors, but sometimes this orderly process breaks down, and abnormal or damaged cells grow and multiply when they shouldn't. When cancer occurs, cells may begin to grow and multiply in an uncontrolled way, resulting in the formation of a mass known as a tumor, if any of these signals are damaged or absent.

The primary tumor is where cancer first appears. Some cancers, like leukemia, attack different parts of the body; in this case, the cancer originates in blood cells. With leukemia, however, tumors do not grow in a clump. Instead, cancer cells accumulate in the blood and, occasionally, the bone marrow.

However, any cell is technically vulnerable to becoming cancerous. While the functions of various cell types in the body vary, their basic functions are pretty much alike.

Every cell has a nucleus, which serves as its command center. Chromosomes, which contain thousands of genes, are located inside the nucleus. Long strands of DNA (deoxyribonucleic acid) are found in genes and serve as coded instructions for making proteins and other molecules.

Genes can be thought of as instructions for producing different products that the cells need. This may be a protein or regulatory molecules that help the cell assemble proteins. RNA. This process helps to control elements such as:

Genes ensure that cells develop and replicate (make copies) in an orderly and controlled manner, which is necessary to maintain the body's wellness.

When a cell divides, the genes can occasionally change. This is called a mutation. Ultimately, this means that a gene has been damaged or changed in some way.

A cell can randomly undergo a mutation while it is dividing. Some mutations result in the cell losing the ability to comprehend its own instructions. It might begin to outgrow control. One mutation is not generally enough to cause cancer. Usually, cancer occurs from multiple mutations over a period of time. That is one reason why cancer occurs more often in older people.

Gene mutations in a specific gene could signify that:

Cancer cells.

A damaged cell can take years to divide, grow, and develop into a tumor large enough to produce symptoms or be detected on a scan.

But what actually causes a cell's genes to mutate?

Since mutations can happen by chance when a cell is dividing, this can result in the cell becoming accidentally cancerous. But, mutations can also occur during the normal functions of cellular life.

Mutations can also be triggered by substances that enter the body from the outside, such as the substances in cigarette smoke. Sometimes, people also inherit genetic flaws that increase their risk of getting cancer.

Every day, some genes are damaged, but cells are quite good at fixing them. But the harm can worsen over time. Additionally, if cells develop too quickly, they are less able to repair the damaged genes and may be more prone to acquiring new mutations.

The first point to note is that not all cancers are fatal.

In England and Wales, for example, 50 out of every 100 (50%) people with cancer survive for ten years or more. In the UK, cancer survivorship is increasing and has doubled in the past 40 years. However, there is a huge variation in ten-year survival rates for different types of cancer, ranging from 98% for testicular cancer to just 1% for pancreatic cancer.

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These are some of the very worst cancers you could ever get - Interesting Engineering

Bone Marrow Stem Cells Comments Off on These are some of the very worst cancers you could ever get – Interesting Engineering | August 26th, 2022

A type of blood cell cancer called angioimmunoblastic T-cell lymphoma (AITL) can develop as mutations accumulate with age in the stem cells from which the T cells in the blood develop.

However, the underlying mechanism by which AITL develops was unknown. Now, a team from the University of Tsukuba in Japan have shown that B cells, another type of blood cells, accumulate mutations in genes that control how the genetic material in the cell is packaged. These aberrant B cells then interact with T cells and lead to the development of AITL.

The paper, Clonal germinal center B cells function as a niche for T-cell lymphoma, was published in the journal Blood.

Blood cells such as B cells and T cells, involved in immunity, develop from stem cells in the bone marrow. Sometimes, mutations occur in individual stem cells that lead to the mutant stem cell giving an increased output of blood cells, all of which carry identical mutations.

The likelihood of this increases with age, known as age-related clonal hematopoiesis, or ACH. ACH is known to be linked to various cancers. AITL, a cancer of the T cells, is linked to ACH with mutations in a gene called TET2. The team used mouse models and human samples to show that theTET2 mutation needed to be present in all blood cells, not just the T cells, for a mouse model to develop AITL.

Using single-cell RNA sequencing, a technique that can show which genes are active within just one cell, they were able to profile the immune cells present in the samples. This revealed a significant increase in the number of aberrant germinal center B cells, a type of B cells with activating and proliferative capacities. These B cells showed recurrent mutations to genes for histone proteins, which organize the genetic material in the cell into higher structures. They also showed alterations to the pattern of a DNA modification called methylation, which affects the genes expressed in the cell.

B cells and T cells can interact through molecules on the cell surface known as CD40 and CD40 ligand.

Analysis of the single-cell sequencing data identified this interaction between CD40 and CD40 ligand as potentially essential for mediating crosstalk between the aberrant B cells and the tumor cells, said lead author Manabu Fujisawa.

Most importantly, the survival of the mice with AITL could be prolonged by treatment with an antibody designed to inhibit CD40 ligand, said main author Mamiko Sakata-Yanagimoto.

The genes expressed in the aberrant mouse GCB cells are also expressed in cells from human AITL withTET2 mutations.

This means that antibodies against CD40 ligand could potentially be a new therapeutic approach to human AITL.

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University of Tsukuba researchers understand the mechanism of AITL - Labiotech.eu

Bone Marrow Stem Cells Comments Off on University of Tsukuba researchers understand the mechanism of AITL – Labiotech.eu | August 26th, 2022