Depending on whats being carried and how much they can pay, the patient or patients involved will choose either a hand-carry service, a commercial carrier such as DHL or FedEx, or something in between, such as the combination of commercial flights and local couriers that Loewen relied on during the pandemic. The cost of transporting my eggs with FlyVet Europa was 1,300 euros, or about $1,400 at the time. That includes the price of two one-way tickets for Paolo and the egg suitcase, and a few incidental expenses. (When I told Monaco how many eggs were traveling, he quipped, Uno squadro di calcio!a soccer team.)

CryoStork, the division of Cryoport devoted to the fertility sector, offers all three tiers of servicecommercial carriers for something that can be easily replaced (sperm, in other words), a middle-tier service using local couriers and air freight, and a door-to-door hand-carry servicefor prices ranging from a few hundred dollars to as much as $7,000 or $8,000 for an international hand-carry trip.

Ultimately, the pandemic boosted business for Loewen. Today, he and a team of eight colleagues, half employees and half working on a per-shipment basis, handle around 30 to 40 IVF-related shipments each month. Similarly, when the war in Ukraine began, Loewen and other colleagues received frantic requests from clients desperate to move their biomaterials out of the capital, Kiev, where most of the countrys IVF clinics and surrogacy agencies are based, and business shifted to nearby Georgia. But by September, Loewen was planning to once again deliver biomaterials to Ukraine. People want to have babiesconflict or not, he says.

What does it take to be a tissue courier, and how does one get into the field? Everyone I spoke to said that to succeed, you must love traveling, have a calm personality (in case, as happened to Loewen, youre ever surrounded by a knot of armed Belarusian soldiers at the airport and accused of trafficking human organs), and be adept at problem-solving.

Loewen looks for people with experience in the travel sector, who can navigate new cities and wont be rattled by a flight cancellation or a grumpy customs official. Mark Sawicki of Cryoport has several former pilots now working as couriers; their security clearances enable them to move through airports more easily than civilians.

Nicole Dorman, 43, has always loved children; she jokes that her current job as a courier is babysitting. She has three kids, aged 14 to 22, and has been a teachers aide and a school crossing guard, following four years in the US Army. When shes home for a week or two at a time with her kids in between gigs, she also makes deliveries for DoorDash in Clarksville, Tennessee.

WENN RIGHTS LTD / ALAMY STOCK PHOTO

Dorman had begun by transporting stem cells for a Frankfurt-based courier service. When she was looking for work in November of 2020, she emailed a half-dozen IVF courier companies and heard back from Loewen within 15 minutes. She has been working for him ever since, and also does US shipments for the Ukrainian company ARK Cryo, as well as EmbryoPort, a UK-based firm.

Dorman is on the road roughly 70% of each month; when we spoke in mid-May, she was preparing for a weeklong trip beginning with a pickup in Indianapolis, a drop-off in Bratislava, a train ride from there to Prague for another pickup, and then a flight to Greece. Like all couriers whove been working for any length of time, she has frequent flier status. In the 18 months since she started, she has transported more than 90 shipments. Now I can pretty much do it in my sleep, she says.

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I took an international trip with my frozen eggs to learn about the fertility industry - MIT Technology Review

Skin Stem Cells Comments Off on I took an international trip with my frozen eggs to learn about the fertility industry – MIT Technology Review | September 19th, 2022

PARIS Barbra Streisand loved her dog Samantha, aka Sammy. The white and fluffy purebred Coton of Tulear was even present on the steps of the Elyse Palace, the French Presidents official residence, when Streisand received the Legion of Honor in 2007.

As the singer and actress explained inThe New York Times in 2018, she loved Sammy so much that, unable to bring herself to see her pass away, she had the dog cloned by a Texas firm for the modest sum of 50,000 dollars just before she died in 2017, at the age of 14. And that's how Barbra Streisand became the happy owner of Miss Violet and Miss Scarlet, two puppies who are the spitting image of the deceased Samantha.

This may sound like a joke, but there is one deeply disturbing fact that Harvard Medical School genetics professor David A. Sinclair points out in his book Why We Age And Why We Dont Have To. It is that the cloning of an old dog has led to two young puppies.

This proves that DNA ours as well as that of Sammy has everything it takes to restore lost youth. This is a property that could be used to "reverse" aging without having to go through the problematic stage of cloning.

The idea rests on identifying the "reset" button of the organism. And aging specialists all have the same piece of good news to announce: this button has been found.

Its name sounds like a Japanese techno-thriller title: "The Yamanaka factors". But Shinya Yamanaka is not a fictional character. He is a scientist specialized in stem cell research who received the 2012 Nobel Prize in Medicine.

If all this sound a bit too science-fictional, you should know that the U.S. biotech company Altos Labs, which was just founded early this year, received a check of three billion dollars from billionaires Yuri Milner and Jeff Bezos. Not bad for a start-up. But this is a start-up with a very promising technology cellular reprogramming, which is nothing more than the name given by biologists to the famous "reset" button.

In 2006-2007, Yamanaka announced to the scientific community that he had discovered a combination of four genes Oct4, Klf4, Sox2 and c-Myc which, when injected into a cell, induces it to go from being a differentiated cell (nerve, blood, and so on) to being a pluripotent stem cell, i.e., one that can subsequently redevelop into any cell type.

It didn't take long for Yamanaka's colleagues to take advantage of his amazing discovery. In 2011, French researcher Jean-Marc Lematre, who worked at the Institute of Functional Genomics at the University of Montpellier (which never received the same financial support as American biotech company Altos Labs!) was the first to experimentally prove, on human tissues, that cellular aging was a reversible process. He and his team succeeded in transforming aging or senescent human skin cells back into young skin cells.

The process has since been improved, since it is no longer necessary to go through the stage of pluripotent cells which can degenerate into cancerous cells to reverse cellular aging. Interrupting the process before reaching this stage is enough to start the series of gene reactions that counter cellular aging.

But that's not all. Since Lematre's pioneering work, biologists from both sides of the Atlantic have shown that what was possible at the level of the cell is also possible at the level of the organism as a whole. As is often the case, they used mice as guinea pigs. At the end of 2016, in a famous study published by the "Cell" magazine, a professor at the Salk Institute (San Diego, California) Juan Carlos Izpisua Belmonte revealed the more than promising results recorded on genetically modified rodents.

The rodents' genome had been enriched with the Yamanaka factors as well as a small piece of additional genetic code, corresponding to a sort of on-off switch. Controlling the activation of the four genes, this "promoter" was itself activated only if the mouse ingested an antibiotic the doxycycline to be precise.

By prescribing this molecule (and thus activating the Yamanaka factors) two days a week throughout the life of the mice, Belmonte and his team increased their lifespan by 40%. "Aging is no longer a unidirectional process, as we thought. We can slow it down and even reverse it," he announced triumphantly. In a very similar experiment, Jean-Marc Lematre has obtained a more modest lengthening, of 15%, but thanks to a single dose of doxycycline. And above all, insists the French researcher, this "extra" lifespan proved to be free of all age-related diseases: osteoporosis, arthritis, pulmonary or renal fibrosis, etc.

The genetic modification of mice is common practice in labs. But should we do the same with humans to get the same result? There was public outcry in 2018 when Chinese researcher He Jiankui gave birth to twins with tampered genomes the first genetically modified children in history with the objective of giving them resistance to HIV.

How we view "GMO babies" may change over the next few decades. But whether it changes or not, it will not be necessary to go that far to do cell reprogramming in humans. A simple vaccine will probably do the trick.

The Covid-19 pandemic made the public aware that a vaccine whether RNA or DNA could be used as a vector to introduce genetic material into the human body. BioNTech's and Moderna's messenger RNA vaccines do this, but many other "viral vectors" exist, such as adeno-associated viruses (AAVs), small, non-pathogenic DNA viruses commonly used in molecular biology to carry one or more "genes of interest. On paper, there is nothing to prevent these genes of interest from being precisely those highlighted by Yamanaka.

And this is what our near future could look like. Around the age of 30, when we are alas, only temporarily! at the peak of our mental and physical fitness, we would receive one or more injections of this viral vector responsible for carrying Yamanaka's factors into us. Nothing would change in our body yet, as the Yamanaka factors have been programmed to remain silent until activated by the promoter. So we would continue to age normally. The passing of the years would no longer be irreparable!

Indeed, as soon as we would start to feel their first undesirable effects, let's say in our mid-forties, we would be prescribed a month's treatment with doxycycline. And then but only then would the youth therapy kick in. White hair disappearing, wounds healing faster, wrinkles fading, organs regenerating, glasses becoming useless... "Like Benjamin Button," writes David Sinclair, "you would experience the sensations of a 35-year-old. Then 30. Then 25. But unlike Benjamin Button, you would not go beyond that limit, because the statute of limitations would be interrupted... You would be about two decades younger biologically, physically and mentally, without having lost any of your knowledge, wisdom or memories."

Of course, such a possibility, if it becomes a reality and especially if it becomes widespread, will revolutionize large parts of society and will not be without its own tricky problems for a resource-limited planet. But who among us, once we reach a certain age, wouldn't dream of regaining our lost youth, while retaining the "benefits of experience"?

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Benjamin Button For Real? Scientists Are Close To Cracking The Code To Reverse Aging - Worldcrunch

Skin Stem Cells Comments Off on Benjamin Button For Real? Scientists Are Close To Cracking The Code To Reverse Aging – Worldcrunch | September 19th, 2022

Sep 17, 2022(Nanowerk News) Few human injuries are as catastrophic as those to the spine. An accident, disease or act of violence affecting the spine can result in poor function even paralysis almost anywhere in the body.The spinal column is enormously complex, with limited capacity for regeneration and any health implications are usually long-term and chronic.While there is no known way to repair a spinal cord injury (SCI), scientists may be on the cusp of some important breakthroughs. New approaches are being taken to reverse the nerve damage, with some researchers attempting to reshape the architecture of the spinal cord using materials engineered in the laboratory.Prof Paula Marques, material scientist at the University of Aveiro in Portugal and her colleagues, are seeking to mould a particular biomaterial into a scaffold that can replace damaged spinal tissue. This will create a working bridge over an injured area giving the brain an alternative pathway to communicate with the body.The hope is that, within the next decade, these biomaterials will result in radical new treatments for the 250-500 000 people who suffer a spinal cord injury around the world every year.Even a small improvement in treatment can lead to a big change to quality of life, said Prof Marques.The spinal column is enormously complex. (Image: CHUTTERSNAP via Unsplash)Nerve regenerationIn addition, the scaffold implant would support the regeneration of natural nerve cells, enabling the body eventually to resume its natural function unassisted.Prof Marques is the principal researcher of the NeuroStimSpinal project, an EIC Pathfinder project under Horizon 2020 focusing on graphene-based material combined with a protein-rich material derived from humans known as a 'decellularised extracellular matrix'. In the human body, an extracellular matrix provides the structure and support to living cells.This blend of matrix and graphene-based material creates a 3D structure that skilfully mimics the morphology of the native spinal cord. It will form the backbone as it were of the projects implant.Graphene shows excellent electrical properties, meaning a current can run along it a prerequisite for any material that might be employed to send electrical impulses along the spinal cord.Importantly, the scaffold is porous, meaning cells and spinal fluids can pass through it. Its also biocompatible, preventing rejection by the body, and biodegradable, allowing it to be programmed to degrade over time.Restoring functionProf Marques describes her work as disruptive and says the potential prize of restoring function to people with paralysis is huge.I see real hope, she said. My only frustration is that we cant move forward faster with this research spinal cord injury has such a big impact on human life.There are two main types of cells in nerve tissue: neurons, which transmit electrical impulses, and glial cells, which are non-conductive and provide a support system for the neurons.In lab experiments, the NeuroStimSpinal team which includes experts in material science, electronic engineering, physics and biology have found that when their scaffold is seeded with embryonic neural progenitor cells (cells that renew themselves and have the potential to develop into either neuronal or glial cells) and an electrical stimulus is applied, the blank stem cells successfully differentiate into a mixture of the two cell types.This is very encouraging, said Prof Marques. It shows that the scaffold can provide a good environment for nerve cell regrowth.Her group is one of just a handful around the world that has managed to make neural stem cells develop into new cell lineages in lab conditions.However, to date, no such success has been achieved in live animals. Prof Marques wants her next round of experiments to set SCI research on a new course.In the months ahead, her team will transplant miniature versions of their scaffold into rats. An electric current will be applied to the implant through a control unit inserted under the animals skin to accelerate tissue regrowth. If these experiments show regeneration of the animals spinal cord is possible with the scaffold in place, Prof Marques will apply for fresh funding to take her work to the next level.I hope we can contribute with our scientific knowledge to take a step forward towards SCI repair, she said.Catastrophic strokeA stroke is another catastrophic life event that can result in damage to the nervous system. Strokes, besides being the number two cause of death worldwide, are the third-leading cause of disability-adjusted life years (DALY), a metric used to assess the burden of death and disease.Scientists have yet to find a way to replace the dead brain cells that result from a clot blocking the flow of blood and oxygen to the brain, but they are starting to exploit the latest technology such as advances in virtual reality (VR) to help patients recover from some of the long-term consequences.After a stroke, hands can become stiff due to disrupted connections between the brain and the hand muscles. This spasticity can make it hard, almost impossible, to straighten fingers or grasp an item.These hand impairments can severely impact daily life, said Dr Joseph Galea, a researcher in motor neuroscience at the University of Birmingham in the UK.Though theres been a lot of focus on improving large, reaching-arm movements after a stroke, theres been little work on improving hand functionality.Dr Galea wants to improve hand-movement recovery through the ImpHandRehab project. With funding from the European Research Council, this project asks stroke patients to perform tasks involving increasingly complex hand movements a form of rehabilitation that will ultimately improve dexterity and quality of life. Users perform their tasks wearing a VR headset paired with affordable, off-the-shelf motion-capture gloves.Demonstration of VR training for stroke treatments. (Video: Joseph Galea)What motivates users to stick to their tasks?Immersive VRGaming, explained Dr Galea. Weve developed two really immersive VR games that reward people for doing better and better at something like popping a balloon or controlling a submarine. Weve noticed that the more points or coins are at stake, the harder a person will try and the better theyll perform.Best of all, he and his colleagues have found that after a game has been played for a prolonged period of time, the improved hand performance persists even when the VR headset is removed.We envisage our solution being used by patients at home, said Dr Galea. It would be complementary to traditional rehab techniques.

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Rehabilitating spinal cord injury and stroke with graphene and gaming - Nanowerk

Spinal Cord Stem Cells Comments Off on Rehabilitating spinal cord injury and stroke with graphene and gaming – Nanowerk | September 19th, 2022

The induced pluripotent stem cells production market has been estimated to reach a CAGR of 8.0% in the foreseeable years from 2021to 2031.

The revenue generation opportunities in the induced pluripotent stem cells production market are attributed to an increased number of R & D activities by numerous organizations and companies to explore iPSCs potential in cell therapeutics that are targeted to treat various diseases.

Induced pluripotent stem cells come with various advantages compared to ESCs (Embryonic Stem Cells), for instance, maximum flexibility in research applications that are based on cells and avoiding the ethical implication associated to stem cells. These advantages of the industry services are likely to contribute to expansion opportunities in the induced pluripotent stem cell production market in the following years.

Increasing uses of iPSCs and robust pipelines for the cell therapeutics that are derived from iPSC have also been projected to serve as revenue generators in the induced pluripotent stem cells production market in the coming years.

In recent years, regenerative medicines are gaining popularity across the globe. In addition to this, iPSCs have been used at an increased rate to regenerate tissue-specific cells to transplant to patients who are experiencing various injuries. The researchers have also been taking an interest to use iPSCs for ex-vivo expansion of different blood components. These factors are likely to contribute to growth opportunities in the induced pluripotent stem cells production market.

Global Induced Pluripotent Stem Cells Market: Overview

Induced pluripotent stem cells (iPSCs) hold profound potential in replacing the use of embryonic stem cells (ESCs) as important tool for drug discovery and development, disease modeling, and transplantation medicine. Advent of new approaches in reprogramming of somatic cells to produce iPSCs have considerably advanced stem cell research, and hence the induced pluripotent stem cells market. The iPSC technology has shown potential for disease modeling and gene therapy in various areas of regenerative medicine. Notable candidates are Parkinsons disease, spinal cord trauma, myocardial infarction, diabetes, leukemia, and heart ailments.

Over the past few years, researchers have come out with several clinically important changes in reprogramming process; a case in point is silencing retroviruses in the human genome. Molecular mechanisms that underlie reprogramming have gained better understanding. However, the tools based on this growing understanding are still in nascent stage. Several factors affect the efficiency of reprogramming, most notably chromosomal instability and tumor expression. These have hindered researchers to utilize the full therapeutic potential of iPSCs, reflecting an unmet need, and hence, a vast potential in the induced pluripotent stemcellsmarket.

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Global Induced Pluripotent Stem Cells Market: Growth Dynamics

The growing application of induced pluripotent stem cells in generating patient-specific stem cells for drug development and human disease models is a key dynamic shaping their demands. Growing focus on personalized regenerative cell therapies among medical researchers and healthcare proponents in various countries have catalyzed their scope of induced pluripotent stem cells market. Advent of new methods to induce safe reprogramming of cells have helped biotechnology companies improve the clinical safety and efficacy of the prevailing stem cells therapies. The relentless pursuit of alternative source of cell types for regenerative therapies has led industry players and the research fraternity to pin hopes on iPSCs to generate potentially a wide range of human cell types with therapeutic potential.

Advances pertaining to better utilizing of retrovirus and lentivirus as reprogramming transcription factors in recent years have expanded the avenue for players in the induced pluripotent stem cells market. Increasing focus on decreasing the clinical difference between ESCs and iPSCs in all its entirety has shaped current research in iPSC technologies, thus unlocking new, exciting potential for biotechnology and pharmaceutical industries.

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Global Induced Pluripotent Stem Cells Market: Notable Development

Over the past few years, fast emerging markets in the global induced pluripotent stem cells are seeing the advent of patents that unveil new techniques for reprogramming of adult cells to reach embryonic stage. Particularly, the idea that these pluripotent stem cells can be made to form any cells in the body has galvanized companies to test their potential in human cell lines. Also, a few biotech companies have intensified their research efforts to improve the safety of and reduce the risk of genetic aberrations in their approved human cell lines. Recently, this has seen the form of collaborative efforts among them.

Lineage Cell Therapeutics and AgeX Therapeutics have in December 2019 announced that they have applied for a patent for a new method for generating iPSCs. These are based on NIH-approved human cell lines, and have been undergoing clinical-stage programs in the treatment of dry macular degeneration and spinal cord injuries. The companies claim to include multiple techniques for reprogramming of animal somatic cells.

Such initiatives by biotech companies are expected to impart a solid push to the evolution of the induced pluripotent stem cells.

Global Induced Pluripotent Stem Cells Market: Regional Assessment

North America is one of the regions attracting colossal research funding and industry investments in induced pluripotent stem cells technologies. Continuous efforts of players to generate immune-matched supply of pluripotent cells to be used in disease modelling has been a key accelerator for growth. Meanwhile, Asia Pacific has also been showing a promising potential in the expansion of the prospects of the market. The rising number of programs for expanding stem cell-based therapy is opening new avenues in the market.

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Induced Pluripotent Stem Cells Market Reaches at a CAGR of 8.0% in the Forecast Periods [2021-2031] - BioSpace

Spinal Cord Stem Cells Comments Off on Induced Pluripotent Stem Cells Market Reaches at a CAGR of 8.0% in the Forecast Periods [2021-2031] – BioSpace | September 19th, 2022

Theaxolotl(Ambystoma mexicanum) is an aquatic salamander renowned for its ability toregenerate its spinal cord, heart and limbs. These amphibians alsoreadily make new neuronsthroughout their lives. In 1964, researchers observed that adult axolotls couldregenerate parts of their brains, even if a large section was completely removed. But one study found that axolotlbrain regenerationhas a limited ability to rebuild original tissue structure.

So how perfectly can axolotls regenerate their brains after injury?

As aresearcher studying regeneration at the cellular level, I and my colleagues in theTreutlein Labat ETH Zurich and theTanaka Labat the Institute of Molecular Pathology in Vienna wondered whether axolotls are able to regenerate all the different cell types in their brain, including the connections linking one brain region to another. In ourrecently published study, we created an atlas of the cells that make up a part of the axolotl brain, shedding light on both the way it regenerates and brain evolution across species.

Differentcell typeshave different functions. They are able to specialize in certain roles because they each express different genes. Understanding what types of cells are in the brain and what they do helps clarify the overall picture of how the brain works. It also allows researchers to make comparisons across evolution and try to find biological trends across species.

One way to understand which cells are expressing which genes is by using a technique calledsingle-cell RNA sequencing (scRNA-seq). This tool allows researchers to count the number of active genes within each cell of a particular sample. This provides a snapshot of the activities each cell was doing when it was collected.

This tool has been instrumental in understanding the types of cells that exist in the brains of animals. Scientists have used scRNA-seq infish,reptiles,miceand evenhumans. But one major piece of the brain evolution puzzle has been missing: amphibians.

Our team decided to focus on thetelencephalonof the axolotl. In humans, the telencephalon is the largest division of the brain and contains a region called theneocortex, which plays a key role in animal behavior and cognition. Throughout recent evolution, the neocortex hasmassively grown in sizecompared with other brain regions. Similarly, the types of cells that make up the telencephalon overall havehighly diversifiedand grown in complexity over time, making this region an intriguing area to study.

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We used scRNA-seq to identify the different types of cells that make up the axolotl telencephalon, including different types ofneuronsandprogenitor cells, or cells that can divide into more of themselves or turn into other cell types. We identified what genes are active whenprogenitor cells become neurons, and found that many pass through an intermediate cell type called neuroblasts previously unknown to exist in axolotls before becoming mature neurons.

We then put axolotl regeneration to the test by removing one section of their telencephalon. Using aspecialized method of scRNA-seq, we were able to capture and sequence all the new cells at different stages of regeneration, from one to 12 weeks after injury. Ultimately, we found that all cell types that were removed had been completely restored.

We observed that brain regeneration happens in three main phases. The first phase starts with a rapid increase in the number of progenitor cells, and a small fraction of these cells activate a wound-healing process. In phase two, progenitor cells begin to differentiate into neuroblasts. Finally, in phase three, the neuroblasts differentiate into the same types of neurons that were originally lost.

Astonishingly, we also observed that the severedneuronal connectionsbetween the removed area and other areas of the brain had been reconnected. This rewiring indicates that the regenerated area had also regained its original function.

Adding amphibians to the evolutionary puzzle allows researchers to infer how the brain and its cell types has changed over time, as well as the mechanisms behind regeneration.

When we compared our axolotl data with other species, we found that cells in their telencephalon show strong similarity to the mammalianhippocampus, the region of the brain involved in memory formation, and theolfactory cortex, the region of the brain involved in the sense of smell. We even found some similarities in one axolotl cell type to the neocortex, the area of the brain known for perception, thought and spatial reasoning in humans. These similarities indicate that these areas of the brain may be evolutionarily conserved, or stayed comparable over the course of evolution, and that the neocortex of mammals may have an ancestor cell type in the telencephalon of amphibians.

While our study sheds light on the process of brain regeneration, including which genes are involved and how cells ultimately become neurons, we still dont know whatexternal signalsinitiate this process. Moreover, we dont know if the processes we identified are still accessible to animals that evolved later in time, such as mice or humans.

But were not solving the brain evolution puzzle alone. TheTosches Labat Columbia University explored the diversity of cell types inanother species of salamander, Pleurodeles waltl, while the Fei lab at the Guangdong Academy of Medical Sciences in China and collaborators at life sciences companyBGIexplored how cell types arespatially arranged in the axolotl forebrain.

Identifying all the cell types in the axolotl brain also helps pave the way for innovative research in regenerative medicine. The brains of mice and humans havelargely lost their capacityto repair or regenerate themselves.Medical interventionsfor severe brain injury currently focus on drug and stem cell therapies to boost or promote repair. Examining the genes and cell types that allow axolotls to accomplish nearly perfect regeneration may be the key to improve treatments for severe injuries and unlock regeneration potential in humans.

This article is republished fromThe Conversationunder a Creative Commons license. Read theoriginalarticle.

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Axolotls can regenerate their brains - Big Think

Spinal Cord Stem Cells Comments Off on Axolotls can regenerate their brains – Big Think | September 19th, 2022

Specially treated stem cells derived from a single individual have been successfully implanted into that same individuals eyes in a first-of-its-kind clinical trial testing ways to treat advanced dry age-related macular degeneration (AMD).

The therapy, currently in its first phase of testing to ensure that its safe for humans, involves harvesting and processing a persons blood cells and using them to replace the persons retinal cells that had succumbed to AMD, a leading cause of vision loss globally.

The procedure was performed by researchers from the National Eye Institute (NEI), a branch of the National Institutes of Health in Bethesda, Maryland, and from the Wilmer Eye Institute at Johns Hopkins School of Medicine in Baltimore. The NIH researchers have been working on the new treatment for a decade.

The scientists, who previously demonstrated the safety and effectiveness of the therapy in rats and pigs, took blood cells from the patient and, in the laboratory, converted them into patient-derived induced pluripotent stem (iPS) cells. These immature, undifferentiated cells have no assigned function in the body, which means they can assume many forms. The researchers programmed these particular iPS cells to become retinal pigment epithelial (RPE) cells, the type that die in AMD and lead to late-stage dry AMD.

In healthy eyes, RPE cells supply oxygen to photoreceptors, the light-sensing cells in the retina at the back of the eyeball. The death of RPE cells virtually dooms the photoreceptors, resulting in vision loss. The idea behind the new therapy is to replace dying RPE cells with patient-derived induced iPS ones, strengthening the health of the remaining photoreceptors.

Before being transplanted, the iPS-derived cells were grown in sheets one cell thick on a biodegradable scaffold designed to promote their integration into the retina. The researchers positioned the resulting patch between atrophied host RPE cells and the photoreceptors using a specially created surgical tool.

The patient received the transplanted cells during the summer and will be followed for a year as researchers monitor overall eye health, including retina stability, and whether any inflammation or bleeding develop, says Kapil Bharti, PhD, a senior investigator at the NEI and for the clinical trial.

Safety data are critical for any new drug, says Gareth Lema, MD, PhD, a vitreoretinal surgeon at New York Eye & Ear Infirmary, a division of the Mount Sinai Health System. Stem cells have added complexity in that they are living tissue, Dr. Lema says. Precise differentiation is necessary for them to fulfill their intended therapeutic effect and not cause harm."

This therapy also requires a surgical procedure to implant the cells, Lema says, adding that its an exquisitely elegant surgery, but introduces further risk of harm. For those reasons, he says, Patients must know that ocular stem cell therapies should only be attempted within the regulated environment of a nationally registered clinical trial.

The rules of a clinical trial dont generally allow specifics to be discussed this early in the process, says Dr. Bharti. Announcing that we were able to successfully transplant the cells now hopefully allows us to recruit more patients, since we can take up to 12 in this phase, he says. We also hope that it will give some optimism to patients with dry AMD and to researchers studying it.

It took seven months to develop the implanted cells, says Bharti, and although the federal Food and Drug Administration (FDA) approved the clinical trial in 2019, the onset of the COVID-19 pandemic delayed the start by two years, he says.

Macular degeneration comprises several stages of disease within the macula, the critical portion of the retina responsible for straight-ahead vision. Aging causes retinal cells to deteriorate, generating debris, or drusen, within the macula, setting the stage for early (aka dry) AMD. Geographic atrophy represents a more advanced stage. If the disease progresses to the relatively rare wet AMD, so named for the leaking of blood into the macula, central vision can be snuffed out.

Risk of AMD increases with age, particularly among people who are white, have a history of smoking, or have a family history of the disease.

Treatment to slow wet AMDs progression includes eye injections with anti-VEGF (or VEGF-A for vascular endothelial growth factor antagonists), a medication that halts the growth of unstable, leaky blood vessels in the eye. Some people may undergo photodynamic therapy, which combines injections and laser treatments.

Currently, there is no cure for dry AMD; it cant be reversed. Nor are there treatments to reliably stop its onset or progression for everyone at every stage of the disease. (Research has confirmed that a specialized blend of vitamins and minerals, available over the counter as AREDS, or Age-Related Eye Disease Studies supplements, reduces the risk of AMDs progression from intermediate to advanced stages.)

There are other, ongoing clinical trials for the treatment of dry AMD. Regenerative Patch Technologies, in Menlo Park, California, for example, is a little further along in testing a different stem cell treatment. Patients have been followed for three years, and 27 percent have shown vision improvement, says Jane Lebkowski, PhD, the companys president. There are a number of AMD clinical trials ongoing in the U.S., and patients should ask their ophthalmologists about trials that might be appropriate.

ClinicalTrials.gov, the NIHs clinical trials database, lists close to 300 AMD clinical trials at various stages in the United States.

Ferhina Ali, MD, MPH, a retinal specialist at the Westchester Medical Center in Valhalla, New York, who isnt involved in the trial, describes the newest stem cell therapy as elegant and pioneering. These are early stages but there is tremendous potential as a first-in-kind surgically implanted stem cell therapy and as a way to achieve vision gains in dry macular degeneration, Dr. Ali says.

Bharti says that in laboratory animals the implanted cells behaved as retinal cells should maintaining the retinas integrity. Over the next few years, he and his colleagues will determine whether they function effectively in humans.

Does that mean, however, that the same AMD disease process that destroyed the original retinal cells could destroy the transplanted ones? It takes 40 to 60 years to damage human cells, Bharti says, and if we get that long with the transplanted cells, well take it.

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Implanting a Patient's Own Reprogrammed Stem Cells Shows Early Positive Results for Treating Dry AMD - Everyday Health

IPS Cell Therapy Comments Off on Implanting a Patient’s Own Reprogrammed Stem Cells Shows Early Positive Results for Treating Dry AMD – Everyday Health | September 19th, 2022

In the present study, we derived two particularly noteworthy results. First, nearly half of the institutions that responded to the study were either currently providing UCB to private banks during the study period or had done so in the past. Second, some institutions were found to provide UCB not only to private banks but also to companies, research institutions, and medical treatment facilities.

During the present study, the APHSCT, along with related ministerial ordinances and guidelines, stipulated how public banks preserve and manage UCB. However, during the study period, these laws and regulations did not require the institutions that handled childbirth to keep records, except when providing UCB to public banks. Consequently, no one knew how many institutions handling childbirth supplied UCB to private banks or the status of UCB distribution. The present study determined that 34.4% of institutions handling childbirth currently provide UCB to private banks, while 16.1% of institutions did so in the past. Our study reported for the first time that these percentages far outstrip those for UCB supply to public banks (6.1% and 8.0%, respectively). These low percentages may be related to the low number of institutions handling childbirth in Japan partnered with public banks (96 institutions as of January 18, 2021) [14,15,16,17,18,19].

However, from the standpoint of appropriate collection, safe preservation, and effective usage of UCB, public and private banks should be regulated according to more uniform standards. More than one-fourth of institutions that provide or have provided UCB to private banks did not provide explanations about UCB collection to UCB donors, while nearly 20% of institutions did not obtain consent. Donors of UCB choose to have their UCB preserved and are also users of UCB who entrust their UCB to private banks, a state of affairs that may lead to the opinion that it is not that important for institutions handling childbirth to provide explanations or obtain consent. However, an MHLW survey reported that private banks do not provide sufficient explanations to users in advance [20]. This state of affairs may be related to the absence of regulations in private banks in Japan.

Even before we demonstrated problems with private banks in Japan in the present study with empirical data, these problems were already known anecdotally, which led many academic associations to issue warnings. In 2002, the Japan Society for Hematopoietic Cell Transplantation issued a statement declaring that private banks were almost completely ineffective, except in cases such as patients with refractory blood diseases within ones own family and that regulations were necessary to ensure proper technical guidelines and safety [21]. In addition, the Japan Association of Obstetricians and Gynecologists declared in 2002 that sufficient understanding was necessary regarding the status and background of private storage of UCB and that careful steps were required to ensure that private banks do not simply use UCB for profit [22].

However, as we analyzed the results of the present study, a relevant concern came to pass. In 2017, physicians who administered UCB to patients without notifying government authorities were found guilty of violating the Act on the Safety of Regenerative Medicine, with the vendor who sold the UCB charged as an accomplice [23, 24]. The UCB sold by the vendor leaked from a private bank that had gone bankrupt in 2009. However, the charge in this case was providing regenerative medicine to patients without reporting it to the MHLW; there was no law targeting the sale of the leaked UCB itself, which was, therefore, beyond the scope of legal penalty [25].

Spurred by the case described above, the MHLW conducted a survey of private UCB banks in Japan [20]. Of the seven vendors whose activities could be confirmed at the time of the survey, six responded; one of these vendors only distributed UCB without preserving it. The UCB held by the remaining five vendors constituted a supply for a total of 45,800 people; roughly 2,100 peoples worth of UCB had not been disposed after the vendors contracts with the donors had ended. One vendor provided UCB to a third party (roughly 160 times). The three vendors involved in the above case later went out of business [26].

Taking the case seriously, the MHLW revised the APHSCT to generally prohibit the collection, preparation, storage, testing, and delivery of UCB for transplantation as a business by entities other than public banks. The revision also stipulated that UCB for transplantation may not be delivered by anyone for commercial purposes. However, these prohibitions do not apply when a public bank delivers UCB, when UCB is used in the treatment of a blood relative to the donor, or when approval is granted by the MHLW. Violations of these prohibitions are subject to criminal penalties. Consequently, the two private banks that obtained approval from the MHLW were permitted to continue their activities.

However, regardless of legal permission, there is still the question of whether private UCB banks, which handle UCB for profit, are ethically permissible. For example, the 2004 European Commissions Group on Ethics in Science and New Technologies stated that while they did not completely disavow for-profit biobank activities, these activities engender ethical criticism. The group also stated that the human body in principle is not an object of commercial value and recommended that private biobank activities operate under strict conditions such as appropriate management by regulatory authorities [27]. Meanwhile, a non-Japanese study has reported that the possibility of UCB being used 20years later by the person who requested its preservation or by their family is an incredibly low 0.040.0005% [28]. The extent to which this information is explained to potential private bank users is unknown. In fact, the previously cited survey by the MHLW indicated that the role of public UCB banks and the actual utility of the UCB stored in the private banks were not sufficiently explained to users [20]. Future research must thoroughly examine the status of UCB private banks following revision of the law and compare the results of this examination to the findings of the present study.

A small number of institutions handling childbirth surveyed in the present study responded that they currently provide or used to provide UCB to medical treatment facilities (2.6%), research institutions (5.9%), companies (2.2%), or foreign medical treatment facilities, research institutions, or companies (0.3%). Some institutions handling childbirth also either currently store or used to store UCB themselves for treatment or research (2.3% and 3.2%, respectively). This aspect of the status of UCB distribution has never been demonstrated in a previous study.

Since the revision of the APHSCT, the delivery of UCB for transplantation has been strictly prohibited except in the cases of provision to a public bank, provision to a private bank approved by the MHLW, and use for treatment by a blood relative. Thus, it is currently considered illegal for institutions handling childbirth to deliver UCB to other facilities domestically or internationally or to store UCB themselves for treatment purposes. However, the revised law still does not apply to the handling of UCB for research purposes, that is, basic studies and the development of treatments. In addition, while there are laws and local ordinances that call for the incineration or burial of UCB according to specific methods, these regulations generallydo not cover the delivery of UCB for research purposes.

At a glance, there would seem to be no problem with an institution that handles childbirth providing UCB to a third party or storing UCB itself for research purposes. However, the results of the present study, which found that a certain number of institutions handling childbirth do not provide explanations or obtain consent when UCB is harvested from private bank users, and the results of the above-cited MHLW survey, which found that private banks also fail to provide users with sufficient explanations, cast doubt amidst the absence of relevant laws and regulations as to how much has been suitably explained to UCB donors when they consent to be third-party UCB donors.

We did not determine what sort of explanations institutions handing childbirth give when they deliver UCB to other institutions or store it themselves for research purposes, nor did we determine methods for obtaining consent, as we felt these fell outside the aim of the present study. Future studies must answer these questions and evaluate if there truly is no problem with the current state of affairs in Japan in the absence of rules regarding the harvest or delivery of UCB for research purposes by institutions handling childbirth.

The present study had several limitations. First, the response rate was only 36.7%, which is not at all high. However, the percentages of institutions handling childbirth by type that responded to our survey are roughly consistent with those of Japanese medical treatment facilities overall [29], implying that our results are representative to some extent. Of course, we cannot rule out the effect of non-responder bias. However, the present study can be considered sufficiently significant because this is the first study to determine the status of UCB delivery by Japanese institutions handling childbirth to private banks, other companies, research institutions, and medical treatment facilities. The 3,277 facilities included in this study represent 99.9% of childbirth facilities in Japan. The total number of facilities in Japan is approximately 3,280. Of which 1,084 facilities responded that they handled childbirth. A simple calculation from the actual number of births in 2016 (976,978 births), a year before this study was conducted [30], allowed us to estimate that the facilities included in our study handled a total of 322,879 births. The number of UCBs managed by these facilities can be considered significant. In addition, by determining the status of UCB delivery prior to revision of the APHSCT, we have made it possible to determine the effects of APHSCT via comparisons with post-revision survey results.

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Current status of umbilical cord blood storage and provision to private biobanks by institutions handling childbirth in Japan - BMC Medical Ethics -...

IPS Cell Therapy Comments Off on Current status of umbilical cord blood storage and provision to private biobanks by institutions handling childbirth in Japan – BMC Medical Ethics -… | September 19th, 2022

Adult stem cells, also called somatic stem cells, are undifferentiated cells that are found in many different tissues throughout the body of nearly all organisms, including humans. Unlike embryonic stem cells, which can become any cell in the body (called pluripotent), adult stem cells, which have been found in a wide range of tissues including skin, heart, brain, liver, and bone marrow are usually restricted to become any type of cell in the tissue or organ that they reside (called multipotent). These adult stem cells, which exist in the tissue for decades, serve to replace cells that are lost in the tissue as needed, such as the growth of new skin every day in humans.

Scientists discovered adult stem cells in bone marrow more than 50 years ago. These blood-forming stem cells have been used in transplants for patients with leukemia and several other diseases for decades. By the 1990s, researchers confirmed that nerve cells in the brain can also be regenerated from endogenous stem cells. It is thought that adult stem cells in a variety of different tissues could lead to treatments for numerous conditions that range from type 1 diabetes (providing insulin-producing cells) to heart attack (repairing cardiac muscle) to neurological disease (regenerating lost neurons in the brain or spinal cord).

Efforts are underway to stimulate these adult stem cells to regenerate missing cells within damaged tissues. This approach will utilize the existing tissue organization and molecules to stimulate and guide the adult stem cells to correctly regenerate only the necessary cell types. Alternatively, the adult stem cells could be isolated from the tissue and grown outside of the body, in cultures. This would allow the cells to be easily manipulated, although they are often relatively rare and difficult to grow in culture.

Because the isolation of adult stem cells does not result in the destruction of human life, research involving adult stem cells does not raise any of the ethical issues associated with research utilizing human embryonic stem cells. Thus, research involving adult stem cells has the potential for therapies that will heal disease and ease suffering, a major focus of Notre Dames stem cell research. Combined with our efforts with induced pluripotent stem (iPS) cells, the Center for Stem Cells and Regenerative Medicine will advance the Universitys mission to ease suffering and heal disease.

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Adult Stem Cells // Center for Stem Cells and Regenerative Medicine ...

Cardiac Stem Cells Comments Off on Adult Stem Cells // Center for Stem Cells and Regenerative Medicine … | September 19th, 2022

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Predicting the risk of acute kidney injury after hematopoietic stem cell transplantation: development of a new predictive nomogram | Scientific...

Bone Marrow Stem Cells Comments Off on Predicting the risk of acute kidney injury after hematopoietic stem cell transplantation: development of a new predictive nomogram | Scientific… | September 19th, 2022

ThisBone Marrow MarketReport provides details on Recent New Developments, Trade Regulations, Import-Export Analysis, Production Analysis, Value Chain Optimization, Market Share, Impact of Domestic and Localized Market Players, Analyzes opportunities in terms of emerging revenue pockets, changing market regulations, strategic market growth analysis, market size, market category growth, niche and application dominance, product endorsements, product launches, geographic expansions , technological innovations in the market.For more information on the bone marrow market, please contact Data Bridge Market Research for a summary of theanalyst, our team will help you make an informed market decision to achieve market growth.

Bone Marrow Market is expected to experience market growth during the forecast period of 2021 to 2028. Data Bridge Market Research analyzes that the market is growing with a CAGR of 5.22% during the forecast period of 2021 to 2028 and it is projected to reach USD 13,899.60 Million by 2028. The increasing number of bone marrow diseases will help accelerate the growth of the bone marrow market.Bone marrow transplant also called hematopoietic stem cell.It is a soft vascular tissue present inside the long bones.It includes two types of stem cells, namely hematopoietic and mesenchymal stem cells.The bone marrow is primarily responsible for hematopoiesis (blood cell formation), lymphocyte production, and fat storage.

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The main factors driving the growth of the bone marrow market during the forecast period are the growth in the incidence of non-Hodgkins and Hodgkins lymphoma, thalassemia, and leukemia, as well as common bone marrow diseases worldwide, developments in technology and improvements.in health infrastructure.In addition, advanced signs of bone marrow transplantation for cardiac and neural disorders, increased funding for logistics services, and rising health care spending per capita are some of the other factors expected to further drive growth. growth of the bone marrow market in the coming years.years.However, the high costs of treatment,

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

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Bone MarrowMarket Scope and Market Size

The bone marrow market is segmented based on transplant type, disease indication, and end user.Growth between these segments will help you analyze weak growth segments in industries and provide users with valuable market overview and market insights to help them make strategic decisions to identify leading market applications.

Country-level analysis of thebone marrow market

The bone marrow market is analyzed and information is provided on market size and trends by country, transplant type, disease indication, and end user, as mentioned above.Countries Covered in Bone Marrow Market Report are USA, Canada, and Mexico, North America, Germany, France, UK, Netherlands, Switzerland, Belgium, Russia, Italy, Spain, Turkey, Rest of Europe in Europe, China, Japan, India, South Korea, Singapore, Malaysia, Australia, Thailand, Indonesia, the Philippines, Rest of Asia-Pacific (APAC) in the Asia-Pacific region (APAC), Saudi Arabia, United Arab Emirates , South Africa, Egypt, Israel, Rest of the Middle East and Africa (MEA) under Middle East and Africa (MEA), Brazil,

Europe dominates the bone marrow market due to the proliferation of innovative health centers.Furthermore, the health systems have introduced bone marrow transplantation in their contributions and state-of-the-art public facilities that will further drive the growth of the bone marrow market in the region during the forecast period.North America is expected to witness significant growth in the bone marrow market due to increasing cases of chronic diseases such as blood cancer.In addition, the increase in the geriatric population is one of the factors that is expected to drive the growth of the bone marrow market in the region in the coming years.

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The country section of the Bone Marrow market report also provides individual market impact factors and regulatory changes in the country market that affect current and future market trends.Data points such as consumption volumes, production sites and volumes, import and export analysis, price trend analysis, raw material cost, Downstream and Upstream value chain analysis are some of the main indicators used to forecast the scenario. of the market for each country.Additionally, the presence and availability of global brands and the challenges they face due to significant or rare competition from local and national brands,

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Bone Marrow market estimated to reach US$13899.60 Million during the forecast period - Digital Journal

Bone Marrow Stem Cells Comments Off on Bone Marrow market estimated to reach US$13899.60 Million during the forecast period – Digital Journal | September 19th, 2022

Louise Herbert flew more than 8,000 miles in January for a risky procedure to slow her MS and says its the best thing shes ever done.

The 41-year-old mum, originally from Shetland, had been a keen runner and netball player before she was diagnosed with the condition at 26.

It caused her immune system to attack itself, at times leaving her so exhausted she could barely spend time with her nine-year-old daughter.

At the start of the year Louisetravelled from her home in Newmachar, Aberdeenshire to Puebla, Mexico for 47,000 haematopoietic stem cell transplantation (HSCT).

Some patients find it does more harm than good causing hair loss, nausea and even infertility and around 3% die from the treatment.

But Louise felt it was a risk worth taking.

During the treatment, doctors took stem cells from Louises bone marrow.

Then used intense chemotherapy to wipe out her immune system, before reintroducing the cells to try and reset her body.

Although Louise did suffer excruciating back pain during her treatment, shes relieved she dodged many of the other side effects.

To be honest, I think I was really lucky because the chemotherapy never made me feel sick, I never felt nauseous or lost my appetite, she explained.

The only thing that really bothered me was these injections we got every morning and every night for a week.

I got horrendous back pain one night, it was so bad I pressed the SOS button on the phones we had to speak to a doctor, she recalled.

Though the back pain was an unpleasant experience, from a medical point of view it was actually a positive.

She said: It was showing there was plenty of stem cells there and they were ready to come out, I think they came out two days later.

One effect of the chemo was that Louises hair fell out but its started to grow back with wild and frizzy curls.

I dont think Ill grow it much beyond my chin, she added.

Though its still too early to be certain, Louise believes there have already been some encouraging signs.

She said: Its still early days, they say its 12 to 18 months before any improvements are seen. Im at seven-and-a-half.

I dont think I can walk any further than before, but I have a bit more confidence in my walking.

I went on the same walk seven times last week, I used to come home and the first thing I wanted to do was sit down in the chair, I wasnt like that last week.

Tasks such as putting on trousers also seems to be less strenuous for Louise than before.

She explained: It was a case I had to lift my left leg up because it couldnt lift itself, its been like that for about five years.

But for the past week Ive noticed I could lift it myself, Ive been going to Pilates which should help improve my balance.

I dont know if its that or the HSCT, but somethings done it.

Im not saying I can lift my leg every day, but if I can do it even three out of seven, thats great.

Upon reflection, Newmachar mum Louise is happy she made the decision to travel to Mexico for this MS treatment.

Im so glad I did it, its the best thing I ever did, youve got to try, she added.

Aberdeen woman with MS to spend 46,000 for stem cell treatment

Aberdeenshire mum says 8,000 mile Mexico trip is only option for her incurable condition

I wanted to see if I still could: MS patient raises charity cash with gruelling challenge

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'Best thing I ever did': Newmachar mum showing promising signs after 47000 MS treatment in Mexico - The Press & Journal

Bone Marrow Stem Cells Comments Off on ‘Best thing I ever did’: Newmachar mum showing promising signs after 47000 MS treatment in Mexico – The Press & Journal | September 19th, 2022

Five people with the autoimmune condition lupus are now in remission after receiving a version of CAR-T therapy, which was originally developed for cancer

By Clare Wilson

Illustration of a CAR-T cell

CHRISTOPH BURGSTEDT/SCIENCE PHOTO LIBRARY

A high-tech cell therapy used to treat cancer has been repurposed as a treatment for lupus, an autoimmune condition that can cause joint, kidney and heart damage.

CAR T-cell therapy has put all five people with lupus treated so far into remission. The participants have been followed up for an average of 8 months, with the first person treated 17 months ago. Thats kind of unheard of, says Chris Wincup at Kings College London, who wasnt involved in the study. This is incredibly exciting.

But it is too soon to know how long the remissions will last, says Georg Schett at the University of Erlangen-Nuremberg in Germany, who was part of the study team.

CAR T-cells were developed to treat blood cancers that arise when B cells, a type of immune cell that normally makes antibodies, start multiplying out of control.

The approach requires taking a sample of immune cells from a persons blood, genetically altering them in the lab so they attack B cells and then infusing them back into the individuals blood. It seems to put 4 out of 10 people with these kinds of cancers into remission.

Lupus, also called systemic lupus erythematosus, is caused by the immune system mistakenly reacting against peoples own DNA. This is driven by B cells making antibodies against DNA released from dying cells.

It is currently treated with medicines that suppress the immune system or, in more severe cases, with drugs that kill B cells. But the treatments cant kill all the B cells, and if the disease flares up badly, some people develop kidney failure and inflammation of their heart and brain.

Schett and his team wondered whether using CAR T-cells to hunt down all the B cells would be more effective. Within three months of receiving the treatment, all five participants were in remission, without needing to take any other medicines to control their symptoms.

The CAR T-cells were barely detectable after one month, and after three and a half months, the volunteers B cells started to return, having been produced by stem cells in bone marrow. These new B cells didnt react against the DNA.

We dont know what normally causes B cells to start reacting against DNA in people with lupus, so it is possible that some kind of trigger may start the process happening again, says Wincup.

The achievement means CAR T-cells may also be useful against other autoimmune diseases that are driven by antibodies, such as multiple sclerosis (MS), in which the immune system attacks nerves, says Schett.

Another radical treatment for MS involves rebooting the immune system by destroying it with chemotherapy. By comparison, CAR T-cells would be less invasive and more tolerable, he says.

But it is too soon to know how effective CAR T-cells will be for autoimmune conditions, says Wincup. This is a small number of patients, so we dont know if this is going to be the result for everyone.

When used in cancer, CAR T-cells are expensive to create for each person, so they may only be used for autoimmune conditions in people with severe disease when no other treatments are available, he says.

Journal reference: Nature Medicine , DOI: 10.1038/s41591-022-02017-5

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Radical lupus treatment uses CAR T-cell therapy developed for cancer - New Scientist

Bone Marrow Stem Cells Comments Off on Radical lupus treatment uses CAR T-cell therapy developed for cancer – New Scientist | September 19th, 2022

Our work on an enzyme that is mutated in leukemia patients has led to the discovery of an entirely new way of regulating this enzyme, as well as new molecules that are more effective and less toxic to human cells, said Norbert Reich, a distinguished professor at the University of California, Santa Barbara, and the corresponding author of the study.

A cells epigenome is copied and maintained by an enzyme called DNMT1. For instance, this enzyme ensures that a dividing liver cell produces two liver cells rather than a brain cell.

However, some cells need to undergo differentiation to become new types of cells. For instance, bone marrow stem cells can developall the various blood cell types, which are incapable of self-replication. DNMT3A, another enzyme, manages this.

This is not a problem until a dysfunction of DNMT3A results in the production of abnormal blood cells from bone marrow. This is a prominent factor in the development of several types of leukemia as well as other cancers.

Most cancer medications are intended to attack cancer cells while only leaving healthy cells. But this is quite a challenging process; therefore, most have severe side effects.

Current leukemia medications, such as Decitabine, bind to DNMT3A in a way that disables it. So that they slow the progression of the disease by obstructing the enzyme's active site, preventing it from continuing its function.

Unfortunately, the active site of DNMT3A is virtually identical to that of DNMT1, therefore, the medication blocks epigenetic regulation in patients' 30 to 40 trillion cells. This leads to off-target toxicity- one of the drug industry's largest bottlenecks.

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Researchers discover a new class of medications that offer a safer treatment for leukemia - Interesting Engineering

Bone Marrow Stem Cells Comments Off on Researchers discover a new class of medications that offer a safer treatment for leukemia – Interesting Engineering | September 19th, 2022

Introduction:Aplastic anemia (AA)is characterized by pancytopenia and hypocellular marrow in the absence of an abnormal infiltrate or increase in reticulin fibrosis. The diagnosis of AA is challenging at times due to decreased cellularity and overlapping morphological features with other bone marrow failure syndromes. Hepatitis-associated aplastic anemia (HAAA) is a rare variant in which patients typically present with jaundice and hepatitis followed by pancytopenia almost within 6 months. Post-hepatitis AA accounts for approximately 1-5%of cases, and invariably such cases are negative for the known hepatitis virus as well. There is limited literature available to understand the correlation of AA with hepatitis with none reported at the national level in our region. As AA is relatively more prevalent in Southeast Asia as compared to the western world and hepatitis is a prevalent disease in our population, the main purpose of this study was to assess the hepatic profile and determine the association of hepatitis in AA at the time of diagnosis.

Materials and methods:A cross-sectional study was carried out at the National Institute of Blood Disease and Bone Marrow Transplantation, Karachi, from November 2019 to December 2020 after the informed consent from patients. The study included all treatment-nave patients of acquired AA with no prior history of taking steroids, immunosuppressive treatment, or chemoradiation therapy. Liver function tests, complete blood count, prothrombin time (PT), and activated partial thromboplastin time were performed, along with viral profiles (HAV, Hep B, Hep C, and HIV). SPSS version 23 (IBM Corp., Armonk, NY) was used for statistical analysis. Mean and standard deviations were computed for quantitative variables while percentages and frequencies were reported for qualitative variables. T-test was used to observe the main difference between groups and a p-value <0.05 was considered to be significant.

Results:Out of a total of 351 patients, 29 (8.2%) patients with AA tested positive for viral hepatitis. Hepatitis A was the most prevalent hepatitis (4.0%), followed by hepatitis C (3.7%). The comparison of platelet counts in patients with and without hepatitis was reported to be of statistical significance (p-value < 0.05). A significant statistical difference (p-value< 0.0001) was found in platelet count and PTin patients of AA with and without hepatitis.

Conclusion:Overall, this study revealed that <10% of patients of AA had a positive screening for hepatitis A, B, and C and low platelet count, and PT was statistically significant when compared between the patients with and without hepatitis. Hepatitis being prevalent in our part of the world might have an important causal association with AA. Patients with AA should be screened for liver functions and viral hepatitis at the time of diagnosis. In addition to hepatitis A, B, and C and HIV, other causes of hepatitis should also be screened such as parvovirus B19, human herpes virus 16, and adenovirus which are not included in routine diagnostic viral testing panel.

The distinctive manifestation(s) of aplastic anemia (AA) are pancytopenia and hypocellular bone marrow without evidence of infiltration, dysplasia, and fibrosis. It is caused by several risk factors including infections, toxins, chemotherapeutic drugs, and radiation but the precise cause remains unclear [1]. An uncommon form of AA known as hepatitis-associated aplastic anemia (HAAA) occurs when pancytopenia develops simultaneously with or within six months after an elevated serum alanine aminotransferase (ALT) level. Significantly, these ALT levels are five times higher than the upper limit of normal. Post-hepatitic AA accounts for approximately 1-5% of cases invariably, and such cases are negative for the known hepatitis virus as well [2].When compared to patients with non-hepatitis-associated AA in the pediatric population, those with HAAA have considerably lower survival and prognosis [3]. Hepatitis symptoms linked to HAAA can be self-limiting, but sometimes showmoderate to severe or acute to the chronic clinical course[4]. Necrosis of the portal region and fibrosis that extends up to the centrilobular area can be found in the transjugular liver biopsy of HAAA patients and chronic severe hepatic inflammation quickly progresses to liver fibrosis [5]. First-line therapies include stem cell transplantation from a sibling donor who matches the patient's human leukocyte antigen (HLA) profile or immunosuppressive therapies like cyclosporine and/or antithymocyte or antilymphocyte globulin [6,7].

The exact etiology of hepatitis causing AA is nearly unknown and the pathogenesis of HAAA has been associated with activated T1 cells [8]. Hepatitis B and C virus, parvovirus B19, human herpes virus 16, and transfusion-transmitted virus (hepatitis B, C, HIV) can all be causal associations. The traits include CD8+-predominant lobular necroinflammatory and endothelial damage associated with sinusoidal obstruction syndrome, conjugated hyperbilirubinemia, elevated antinuclear antibody titers, and elevated transaminases [9]. Dietary or nutrition supplements at times may also result in toxin-induced hepatitis [10].It is typical for intrabiliary cholestasis and liver toxicity to result in the apoptotic killing of hematopoietic cells by CD8 lymphocytes and T cell-induced gamma interferon, which leads to hepatitis. Clinical symptoms include pallor, exhaustion, petechial rash, and infections due to pancytopenia [11]. When severe thrombocytopenia and anemia appear at the same time as HAAA, it is important to distinguish this condition from infantile giant cell hepatitis with autoimmune hemolytic anemia [12].

Allogeneic bone marrow transplantation (allo BMT) is the conventional curative treatment for HAAA from an HLA-matched donor. Since HAAA has a poor prognosis, allo BMT has been the curative form of treatment [13-15]. On the other hand, immunosuppressive medication results in a response rate of 70% and a survival rate of 85% for patients not receiving hematopoietic cell transplantation, respectively [16]. Children respond to BMT better than adults do, and the survival rates of patients receiving bone marrow from HLA-matched donors are found to be comparable to that of the patients with AA not caused by hepatitis [17]. There is no recognized antiviral medication for hepatitis B-related HAAA. Lamivudine, a nucleoside analog, has been studied for use in treating hepatitis B-related HAAA, and it has been shown to be effective in causing remission in cases of severe AA and hepatitis B virus infection. Because of its myelosuppressive effects, interferon, an acclaimed antiviral agent in the treatment arsenal of HBV- and HCV-mediated infections, cannot be used as a treatment option for the HAAA [18]. Patients with HAAA exhibit severe pancytopenia following an episode of acute hepatitis, and if left untreated, the marrow suppression is frequently swift and severe.

In Pakistan, cases of hepatitis have been increasing over time, and given the current policies and practices, eradicating hepatitis from Pakistan by 2030 seems unreasonable[19]. We have also noted a rising trend in the incidence of AA than reported internationally. The association of hepatitis with AA is underreported and limited literature is available regarding the determinants of AA. Hepatitis might be one of the causes of AA and it must be considered an alarming situation.The only curative option for AA is BMT, which is an unaffordable treatment option for many patients in Pakistan. Therefore, the aim to conduct this study was to evaluate the hepatic status in relation to hepatitis in treatment-nave AA patients.

This was a cross-sectional study carried out at the National Institute of Blood Diseases and Bone Marrow Transplantation (NIBD & BMT). Patients were recruited between November 2019 and December 2021. Prior to the initiation of the study, approval was taken from the NIBD ethics committee bearing NIBD/RD-188/11-2019 and informed consent was taken from the participants prior to enrollment in the study. The study included all treatment-nave patients of acquired AA with no prior history of taking steroids, immunosuppressive treatment, or chemoradiation therapy. Patients with positive chromosomal breaks (Fanconis anemia) or inherited bone marrow failure were excluded. WHO sample size calculator was used to calculate the sample size, and by taking the percentage reported in the literature (5%) [14] it was found to be at least 73, and hence we recruited 351 patients who visited during the study duration.Non-probability purposive sampling method was used for patient selection. Demographicand laboratory parameters were recorded through a structured questionnaire and the diagnosis of AA was confirmed on bone marrow biopsy. Liver function tests (LFTs), complete blood count (CBC), prothrombin time (PT), and activated partial thromboplastin time (APTT) were performed. PT and APTT were run on STAGO and Sysmex CA-1500, and CBC was performed using a Sysmex XN-1000 analyzer from the Sysmex Corporation in Kobe, Japan. LFTs were performed on a Cobas C 111 analyzer machine that runs on a spectrophotometer principle.Within 2 hours of the blood sample collection, an aseptic setting was used to take a 4 ml blood sample from each patient, which was then tested for the presence of hepatitis A, HBV, HCV, and HIV. Detection of hepatitis B surface antigen and anti-hepatitis C antibodies was done using the chemiluminescence technique. To confirm chronic HCV and HBV infection in individuals with positive antibody tests, a qualitative nucleic acid test was employed as the initial diagnosis of a suspected acute infection. Ultrasound was done to complement the diagnosis of hepatitis. The data were entered in MS Excel and analysis was done by using Statistical Package for Social Sciences (SPSS) version 23.0 (IBM Corp., Armonk, NY). Shapiro-Wilk test was performed for normality and data were found normally distributed. Mean and standard deviations were computed for quantitative variables and percentages and frequencies were reported for qualitative variables. T-test was used to observe the mean difference between the two groups and a p-value <0.05 was found to be significant statistically.

A total of 351 patients were enrolled, out of which 222 (63%) were males, 265 (76%) were unmarried, 11 (3.1%)had hypertension, and 9 (2.5%) had diabetes. The mean age of participants was 30.9 27.5. Twenty-nine (8.2%) patients with AA had hepatitis. The most common hepatitis was hepatitis A, 14 (4.0%), followed by hepatitis C, 13 (3.7%). The most common form of hepatitis C was acute 9 (69.2%). Two patients had compensated cirrhosis and two patients had decompensated cirrhosis (Table 1).

The association of CBC parameters such as hemoglobin, red blood cell count, packed cell volume, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, total leukocyte count, neutrophils, lymphocytes, monocytes, and platelets with the patients with and without hepatitis was assessed and it was found out that platelet counts were statistically significant (p-value: 0.0020) as shown in Table 2.

Table 3 depicts the association of liver profile such as serum glutamate pyruvate transaminase, gamma glutamyl transferase (GGT), serum glutamic oxaloacetic acid transaminase, PT, APTT, and international normalized ratio with the patients with and without hepatitis, and it was found out that PT (p-value< 0.0001) was statistically significant.

In our study, 8.2% of AA patients had hepatitis. This is comparatively high as compared to theprevalence of hepatitis in the general population in Pakistan, which is reported to be around 4% [20]. A retrospective study carried out in Europe from 1997 to 2007 demonstrated that HAAA patients had a slight male predominance with a value of 68% [21], which is close to the prevalence of male participants in our study, i.e. 63.2%. This European study also demonstrated that there was no causative virus for hepatitis in 94% of HAAA patients. However, 15 patients (6%) had hepatitis with nine having hepatitis B virus and six having hepatitis A virus [21]. Similar results have been observed in our study with 91.4% HAAA serologically negative and not having any signs or symptoms of hepatitis. Twenty-nine patients (8.3%) had evidence of hepatitis: hepatitis A virus in 14 patients, hepatitis B virus in 2, and hepatitis C virus in 13 patients. Assessing the association of hepatitis C virus with HAAA, a study conducted in France showed that 15.8% of HAAA patients had hepatitis C virus [22], which was approximately three-fold higher compared to our study suggesting a prevalence of 3.7% of HAAA patients with hepatitis C virus. On the contrary, slightly similar figures were recreated in another comparative study done in Thailand which showed that 5.7% of the patients who were never transfusedwere found to have hepatitis C virus [23].

During the initial course of hepatitis, cytotoxic T lymphocytes (CTLs) occupy the same receptor antigen between liver and bone marrow cells. These CTLs replicate and extend to destroy bone marrow hematopoietic stem cells and result in AA [24,25].However, another interesting finding of our study was that AA patients with hepatitis had considerably high platelet counts compared to those without hepatitis (29 28 vs 4 3). This finding is also in concordance with a study conducted by Wang WH et al. [3] in which the HAAA group had a considerably higher platelet count compared to the non-hepatitis-associated AA (50 109/L vs 12 109/L).

Literature reveals that amongthe most frequently assessed values in HAAA, there is a significant rise in ALT, GGT, and serum alkaline phosphatase [26]. The elevated levels are also shown in our results (Table 3). Considerable discrepancies were observed in PT in AA patients with and without hepatitis. This could be on account of viral hepatitis causing deranged LFTs [27].However, studies comparing the levels of liver enzymes between hepatitis-associated and non-hepatitis-associated AA are not extensively reported in the literature.

To the best of our knowledge, this is the first study at the national level to determine the association of hepatitis in patients with AA. However, the limitations of our study were that it was of cross-sectional nature and included non-probability sampling. Prospective cohort studies with stringent inclusion and exclusion criteria, a large sample size, and a controlled environment are needed to validate the findings.

AA is a heterogeneous disease with a limited approach to curative treatment options like allogeneic stem cell transplant in our region. Hepatitis being prevalent in our part of the world might have an important causal association with AA. Patients should be screened for viral hepatitis at the time of diagnosis. Moreover, other causes of hepatitis should also be screened at the time of diagnosis such as parvovirus B19, human herpes virus 16, and adenovirus. Based on the rapidly advancing research methodologies, it is necessary to comprehensively analyze the underlying mechanisms of HAAA.

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Assessment of Hepatic Profile in Acquired Aplastic Anemia: An Experience From Pakistan - Cureus

Bone Marrow Stem Cells Comments Off on Assessment of Hepatic Profile in Acquired Aplastic Anemia: An Experience From Pakistan – Cureus | September 19th, 2022

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CCL7 as a novel inflammatory mediator in cardiovascular disease, diabetes mellitus, and kidney disease - Cardiovascular Diabetology - Cardiovascular...

Cardiac Stem Cells Comments Off on CCL7 as a novel inflammatory mediator in cardiovascular disease, diabetes mellitus, and kidney disease – Cardiovascular Diabetology – Cardiovascular… | September 19th, 2022

Positive Opinion Based on Landmark ZUMA-7 Study in Which 41% of Patients Demonstrated Event-Free Survival at Two Years versus 16% for Standard of Care -

SANTA MONICA, Calif.--(BUSINESS WIRE)--Kite, a Gilead Company (Nasdaq: GILD), today announces that the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for Yescarta (axicabtagene ciloleucel) for adult patients with diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) that relapses within 12 months from completion of, or is refractory to, first-line chemoimmunotherapy. If approved, Yescarta will be the first Chimeric Antigen Receptor (CAR) T-cell therapy approved for patients in Europe who do not respond to first-line treatment. Although 60% of newly diagnosed LBCL patients will respond to their initial treatment, 40% will relapse or will not respond and need 2nd line treatment.

At Kite, we are committed to bringing the curative potential of cell therapy to the world, and changing the way cancer is treated, said Christi Shaw, CEO, Kite. Todays positive CHMP opinion brings us a step closer to utilizing cell therapy earlier in the treatment journey, potentially transforming the standard of care for the most common and aggressive form of non-Hodgkin lymphoma.

The European Commission will review the CHMP opinion, and a final decision on the marketing authorization is expected in the coming months.

For people with DLBCL and HGBL who do not respond to first-line treatment or have an early relapse, outcomes are often poor and there are limited curative treatment options for these patients, said Marie Jos Kersten, Professor of Hematology at Amsterdam University Medical Centers, Amsterdam. If approved, axicabtagene ciloleucel may offer a new standard of care for patients with relapsed or refractory DLBCL and HGBL. Importantly, in a randomized trial of axicabtagene ciloleucel versus the current standard of care, quality of life also showed greater improvement in the experimental arm.

The positive opinion for Yescarta is based on the primary results of the landmark Phase 3 ZUMA-7 study, the largest and longest trial of a CAR T-cell therapy versus standard of care (SOC) in second-line LBCL. Results demonstrated that at a median follow-up of two years, Yescarta-treated patients had a four-fold greater improvement in the primary endpoint of event-free survival (EFS; hazard ratio 0.40; 95% CI: 0.31-0.51, P<0.001) over the current SOC (8.3 months v 2.0 months). Additionally, Yescarta demonstrated a 2.5 fold increase in patients who were alive at two years without disease progression or need for additional cancer treatment vs SOC (41% v 16%). Improvements in EFS with Yescarta were consistent across key patient subgroups, including elderly patients (HR: 0.28 [95% CI: 0.16-0.46]), primary refractory patients (HR: 0.43 [95% CI: 0.32- 0.57]), high-grade B cell lymphoma including double-hit and triple-hit lymphoma patients (HGBL; HR: 0.28 [95% CI: 0.14-0.59]), and double expressor lymphoma patients (HR: 0.42 [95% CI: 0.27-0.67]).

In a separate, secondary analysis of Patient-Reported Outcomes (PROs) published in Blood patients receiving Yescarta and eligible for the PROs portion of the study (n=165) showed statistically significant improvements in Quality of Life (QoL) at Day 100 compared with those who received SOC (n=131), using a pre-specified analysis for three PRO-domains (EORTC QLQ-C30 Physical Functioning, EORTC QLQ-C30 Global Health Status/QOL, and EQ-5D-5L visual analog scale [VAS]). There was also a trend toward faster recovery to baseline QoL in the Yescarta arm versus SOC.

In the ZUMA-7 trial, Yescarta had a manageable safety profile that was consistent with previous studies. Among the 170 Yescarta-treated patients evaluable for safety, Grade 3 cytokine release syndrome (CRS) and neurologic events were observed in 6% and 21% of patients, respectively. No Grade 5 CRS or neurologic events occurred. In the SOC arm, 83% of patients had high-grade events, mostly cytopenias (low blood counts).

About ZUMA-7

ZUMA-7 is an ongoing, randomized, open-label, global, multicenter (US, Australia, Canada, Europe, Israel) Phase 3 study of 359 patients at 77 centers, evaluating the safety and efficacy of a single-infusion of Yescarta versus current SOC for second-line therapy (platinum-based salvage combination chemotherapy regimen followed by high-dose chemotherapy and autologous stem cell transplant in those who respond to salvage chemotherapy) in adult patients with relapsed or refractory LBCL within 12 months of first-line therapy. The primary endpoint is event free survival (EFS) as determined by blinded central review, and defined as the time from randomization to the earliest date of disease progression per Lugano Classification, commencement of new lymphoma therapy, or death from any cause. Key secondary endpoints include objective response rate (ORR) and overall survival (OS). Additional secondary endpoints include patient reported outcomes (PROs) and safety.

About Yescarta

Yescarta was first approved in Europe in 2018 and is currently indicated for three types of blood cancer: Diffuse Large B-Cell Lymphoma (DLBCL); Primary Mediastinal Large B-Cell Lymphoma (PMBCL); and Follicular Lymphoma (FL). For the full European Prescribing Information, please visit: https://www.ema.europa.eu/en/medicines/human/EPAR/yescarta

Please see full US Prescribing Information, including BOXED WARNING and Medication Guide.

YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:

U.S. IMPORTANT SAFETY INFORMATION

BOXED WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITIES

CYTOKINE RELEASE SYNDROME (CRS)

CRS, including fatal or life-threatening reactions, occurred. CRS occurred in 90% (379/422) of patients with non-Hodgkin lymphoma (NHL), including Grade 3 in 9%. CRS occurred in 93% (256/276) of patients with large B-cell lymphoma (LBCL), including Grade 3 in 9%. Among patients with LBCL who died after receiving YESCARTA, 4 had ongoing CRS events at the time of death. For patients with LBCL in ZUMA-1, the median time to onset of CRS was 2 days following infusion (range: 1-12 days) and the median duration was 7 days (range: 2-58 days). For patients with LBCL in ZUMA-7, the median time to onset of CRS was 3 days following infusion (range: 1-10 days) and the median duration was 7 days (range: 2-43 days). CRS occurred in 84% (123/146) of patients with indolent non-Hodgkin lymphoma (iNHL) in ZUMA-5, including Grade 3 in 8%. Among patients with iNHL who died after receiving YESCARTA, 1 patient had an ongoing CRS event at the time of death. The median time to onset of CRS was 4 days (range: 1-20 days) and the median duration was 6 days (range: 1-27 days) for patients with iNHL.

Key manifestations of CRS ( 10%) in all patients combined included fever (85%), hypotension (40%), tachycardia (32%), chills (22%), hypoxia (20%), headache (15%), and fatigue (12%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), renal insufficiency, cardiac failure, respiratory failure, cardiac arrest, capillary leak syndrome, multi-organ failure, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome.

The impact of tocilizumab and/or corticosteroids on the incidence and severity of CRS was assessed in 2 subsequent cohorts of LBCL patients in ZUMA-1. Among patients who received tocilizumab and/or corticosteroids for ongoing Grade 1 events, CRS occurred in 93% (38/41), including 2% (1/41) with Grade 3 CRS; no patients experienced a Grade 4 or 5 event. The median time to onset of CRS was 2 days (range: 1-8 days) and the median duration of CRS was 7 days (range: 2-16 days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3 days beginning on the day of infusion of YESCARTA. Thirty-one of the 39 patients (79%) developed CRS and were managed with tocilizumab and/or therapeutic doses of corticosteroids with no patients developing Grade 3 CRS. The median time to onset of CRS was 5 days (range: 1-15 days) and the median duration of CRS was 4 days (range: 1-10 days). Although there is no known mechanistic explanation, consider the risk and benefits of prophylactic corticosteroids in the context of pre-existing comorbidities for the individual patient and the potential for the risk of Grade 4 and prolonged neurologic toxicities.

Ensure that 2 doses of tocilizumab are available prior to YESCARTA infusion. Monitor patients for signs and symptoms of CRS at least daily for 7 days at the certified healthcare facility, and for 4 weeks thereafter. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated.

NEUROLOGIC TOXICITIES

Neurologic toxicities (including immune effector cell-associated neurotoxicity syndrome) that were fatal or life-threatening occurred. Neurologic toxicities occurred in 78% (330/422) of all patients with NHL receiving YESCARTA, including Grade 3 in 25%. Neurologic toxicities occurred in 87% (94/108) of patients with LBCL in ZUMA-1, including Grade 3 in 31% and in 74% (124/168) of patients in ZUMA-7 including Grade 3 in 25%. The median time to onset was 4 days (range: 1-43 days) and the median duration was 17 days for patients with LBCL in ZUMA-1. The median time to onset for neurologic toxicity was 5 days (range:1- 133 days) and the median duration was 15 days in patients with LBCL in ZUMA-7. Neurologic toxicities occurred in 77% (112/146) of patients with iNHL, including Grade 3 in 21%. The median time to onset was 6 days (range: 1-79 days) and the median duration was 16 days. Ninety-eight percent of all neurologic toxicities in patients with LBCL and 99% of all neurologic toxicities in patients with iNHL occurred within the first 8 weeks of YESCARTA infusion. Neurologic toxicities occurred within the first 7 days of infusion for 87% of affected patients with LBCL and 74% of affected patients with iNHL.

The most common neurologic toxicities ( 10%) in all patients combined included encephalopathy (50%), headache (43%), tremor (29%), dizziness (21%), aphasia (17%), delirium (15%), and insomnia (10%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events, including aphasia, leukoencephalopathy, dysarthria, lethargy, and seizures occurred. Fatal and serious cases of cerebral edema and encephalopathy, including late-onset encephalopathy, have occurred.

The impact of tocilizumab and/or corticosteroids on the incidence and severity of neurologic toxicities was assessed in 2 subsequent cohorts of LBCL patients in ZUMA-1. Among patients who received corticosteroids at the onset of Grade 1 toxicities, neurologic toxicities occurred in 78% (32/41), and 20% (8/41) had Grade 3 neurologic toxicities; no patients experienced a Grade 4 or 5 event. The median time to onset of neurologic toxicities was 6 days (range: 1-93 days) with a median duration of 8 days (range: 1-144 days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3 days beginning on the day of infusion of YESCARTA. Of those patients, 85% (33/39) developed neurologic toxicities, 8% (3/39) developed Grade 3, and 5% (2/39) developed Grade 4 neurologic toxicities. The median time to onset of neurologic toxicities was 6 days (range: 1-274 days) with a median duration of 12 days (range: 1-107 days). Prophylactic corticosteroids for management of CRS and neurologic toxicities may result in a higher grade of neurologic toxicities or prolongation of neurologic toxicities, delay the onset of and decrease the duration of CRS.

Monitor patients for signs and symptoms of neurologic toxicities at least daily for 7 days at the certified healthcare facility, and for 4 weeks thereafter, and treat promptly.

REMS

Because of the risk of CRS and neurologic toxicities, YESCARTA is available only through a restricted program called the YESCARTA and TECARTUS REMS Program which requires that: Healthcare facilities that dispense and administer YESCARTA must be enrolled and comply with the REMS requirements and must have on-site, immediate access to a minimum of 2 doses of tocilizumab for each patient for infusion within 2 hours after YESCARTA infusion, if needed for treatment of CRS. Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer YESCARTA are trained in the management of CRS and neurologic toxicities. Further information is available at http://www.YescartaTecartusREMS.com or 1-844-454-KITE (5483).

HYPERSENSITIVITY REACTIONS

Allergic reactions, including serious hypersensitivity reactions or anaphylaxis, may occur with the infusion of YESCARTA.

SERIOUS INFECTIONS

Severe or life-threatening infections occurred. Infections (all grades) occurred in 45% of patients with NHL; Grade 3 infections occurred in 17% of patients, including Grade 3 infections with an unspecified pathogen in 12%, bacterial infections in 5%, viral infections in 3%, and fungal infections in 1%. YESCARTA should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after infusion and treat appropriately. Administer prophylactic antimicrobials according to local guidelines.

Febrile neutropenia was observed in 36% of all patients with NHL and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care as medically indicated.

In immunosuppressed patients, including those who have received YESCARTA, life-threatening and fatal opportunistic infections including disseminated fungal infections (e.g., candida sepsis and aspergillus infections) and viral reactivation (e.g., human herpes virus-6 [HHV-6] encephalitis and JC virus progressive multifocal leukoencephalopathy [PML]) have been reported. The possibility of HHV-6 encephalitis and PML should be considered in immunosuppressed patients with neurologic events and appropriate diagnostic evaluations should be performed.

Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells, including YESCARTA. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

PROLONGED CYTOPENIAS

Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and YESCARTA infusion. Grade 3 cytopenias not resolved by Day 30 following YESCARTA infusion occurred in 39% of all patients with NHL and included neutropenia (33%), thrombocytopenia (13%), and anemia (8%). Monitor blood counts after infusion.

HYPOGAMMAGLOBULINEMIA

B-cell aplasia and hypogammaglobulinemia can occur. Hypogammaglobulinemia was reported as an adverse reaction in 14% of all patients with NHL. Monitor immunoglobulin levels after treatment and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement. The safety of immunization with live viral vaccines during or following YESCARTA treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during YESCARTA treatment, and until immune recovery following treatment.

SECONDARY MALIGNANCIES

Secondary malignancies may develop. Monitor life-long for secondary malignancies. In the event that one occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES

Due to the potential for neurologic events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following YESCARTA infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

ADVERSE REACTIONS

The most common non-laboratory adverse reactions (incidence 20%) in patients with LBCL in ZUMA-7 included fever, CRS, fatigue, hypotension, encephalopathy, tachycardia, diarrhea, headache, musculoskeletal pain, nausea, febrile neutropenia, chills, cough, infection with an unspecified pathogen, dizziness, tremor, decreased appetite, edema, hypoxia, abdominal pain, aphasia, constipation, and vomiting.

The most common adverse reactions (incidence 20%) in patients with LBCL in ZUMA-1 included CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections with an unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias.

The most common non-laboratory adverse reactions (incidence 20%) in patients with iNHL in ZUMA-5 included fever, CRS, hypotension, encephalopathy, fatigue, headache, infections with an unspecified, tachycardia, febrile neutropenia, musculoskeletal pain, nausea, tremor, chills, diarrhea, constipation, decreased appetite, cough, vomiting, hypoxia, arrhythmia, and dizziness.

About Kite

Kite, a Gilead Company, is a global biopharmaceutical company based in Santa Monica, California, with manufacturing operations in North America and Europe. Kites singular focus is cell therapy to treat and potentially cure cancer. As the cell therapy leader, Kite has more approved CAR T indications to help more patients than any other company. For more information on Kite, please visit http://www.kitepharma.com. Follow Kite on social media on Twitter (@KitePharma) and LinkedIn.

About Gilead Sciences

Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statements

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the ability of Gilead and Kite to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing and additional clinical trials, including those involving Yescarta; uncertainties relating to regulatory applications and related filing and approval timelines, including the risk that the European Commission may not grant marketing authorization for Yescarta for use in second-line DLBCL and HGBL in a timely manner or at all; the risk that any regulatory approvals, if granted, may be subject to significant limitations on use; the risk that physicians may not see the benefits of prescribing Yescarta for the treatment of LBCL; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and other factors are described in detail in Gileads Quarterly Report on Form 10-Q for the quarter ended June 30, 2022 as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead and Kite, and Gilead and Kite assume no obligation and disclaim any intent to update any such forward-looking statements.

U.S. Prescribing Information for Yescarta including BOXED WARNING, is available at http://www.kitepharma.com and http://www.gilead.com .

Kite, the Kite logo, Yescarta and GILEAD are trademarks of Gilead Sciences, Inc. or its related companies .

View source version on businesswire.com: https://www.businesswire.com/news/home/20220916005209/en/

Jacquie Ross, Investorsinvestor_relations@gilead.com

Anna Padula, Mediaapadula@kitepharma.com

Source: Gilead Sciences, Inc.

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Cardiac Stem Cells Comments Off on Kite’s CAR T-cell Therapy Yescarta First in Europe to Receive Positive CHMP Opinion for Use in Second-line Diffuse Large B-cell Lymphoma and… | September 19th, 2022

IMAC Holdings, Inc.

BRENTWOOD, Tenn., Sept. 09, 2022 (GLOBE NEWSWIRE) -- IMAC Holdings, Inc. (Nasdaq: BACK) (IMAC or the Company), today announces it has completed the third cohort of its Phase 1 clinical trial for its investigational compound utilizing umbilical cord-derived allogenic mesenchymal stem cells for the treatment of bradykinesia due to Parkinsons disease.

The third cohort consists of five patients with bradykinesia due to Parkinsons disease receiving an intravenous infusion of a high concentration stem cell treatment. The third and final cohort of the Phase 1 clinical trial was completed on Tuesday, September 6, 2022.

About IMACs Phase 1 Clinical Trial

The Phase 1 clinical trial, consisting of a 15-patient dose escalation safety and tolerability study, is being conducted at three of IMACs clinical centers in Chesterfield, Missouri, Paducah, Kentucky, and Brentwood, Tennessee. The trial is divided into three groups: 1) five patients with bradykinesia due to Parkinsons disease received a low concentration dose, intravenous infusion of stem cells, 2) five received a medium concentration intravenous dose, 3) and five received a high concentration intravenous dose. All groups will be subsequently tracked for 12 months. IMACs medical doctors and physical therapists at the clinical sites have been trained to administer the treatment and manage the therapy. Ricardo Knight, M.D., M.B.A., who is medical director of the IMAC Regeneration Center of Chicago, is the trials principal investigator.

The Institute of Regenerative and Cellular Medicine serves as the trials independent investigational review board, while Regenerative Outcomes provides management of the study. Further details of the trial can be found at clinicaltrials.gov.

About Bradykinesia Due to Parkinsons Disease

In addition to unusually slow movements and reflexes, bradykinesia may lead to limited ability to lift arms and legs, reduced facial expressions, rigid muscle tone, a shuffling walk, and difficulty with repetitive motion tasks, self-care, and daily activities. Parkinsons disease is the typical culprit of bradykinesia, and as it progresses through its stages, a persons ability to move and respond declines.

Story continues

According to Zion Market Research, the global Parkinsons disease therapeutics market was $2.61 billion in 2018 and is expected to grow to $5.28 billion by 2025. The Parkinsons Disease Foundation estimates that nearly 10 million people are suffering from Parkinsons disease, and almost 60,000 new cases are reported annually in the U.S.

About IMAC Holdings, Inc.

IMAC Holdingsowns and manages health and wellness centers that deliver sports medicine, orthopedic care, and restorative joint and tissue therapies for movement restricting pain and neurodegenerative diseases.IMACis comprised of three business segments: outpatient medical centers, The Back Space, and a clinical research division. With treatments to address both young and aging populations,IMAC Holdingsowns or manages outpatient medical clinics that deliver regenerative rehabilitation services as a minimally invasive approach to acute and chronic musculoskeletal and neurological health problems. IMACs The Back Company retail spinal health and wellness treatment centers deliver chiropractic care within Walmart locations. IMACs research division is currently conducting a Phase I clinical trial evaluating a mesenchymal stem cell therapy candidate for bradykinesia due to Parkinsons disease. For more information visitwww.imacholdings.com.

# # #

Safe Harbor Statement

This press release contains forward-looking statements. These forward-looking statements, and terms such as anticipate, expect, believe, may, will, should or other comparable terms, are based largely on IMAC's expectations and are subject to a number of risks and uncertainties, certain of which are beyond IMAC's control. Actual results could differ materially from these forward-looking statements as a result of, among other factors, risks and uncertainties associated with its ability to raise additional funding, its ability to maintain and grow its business, variability of operating results, its ability to maintain and enhance its brand, its development and introduction of new products and services, the successful integration of acquired companies, technologies and assets, marketing and other business development initiatives, competition in the industry, general government regulation, economic conditions, dependence on key personnel, the ability to attract, hire and retain personnel who possess the skills and experience necessary to meet customers requirements, and its ability to protect its intellectual property. IMAC encourages you to review other factors that may affect its future results in its registration statement and in its other filings with the Securities and Exchange Commission. In light of these risks and uncertainties, there can be no assurance that the forward-looking information contained in this press release will in fact occur.

IMAC Press Contact:

Laura Fristoe

lfristoe@imacrc.com

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IMAC Holdings, Inc. Announces Completion of Third Cohort of its Phase 1 Clinical Study of Umbilical Cord-Derived Mesenchymal Stem Cells for the...

Spinal Cord Stem Cells Comments Off on IMAC Holdings, Inc. Announces Completion of Third Cohort of its Phase 1 Clinical Study of Umbilical Cord-Derived Mesenchymal Stem Cells for the… | September 11th, 2022

A person with SMA may find it challenging to stand up, walk, control their head movements, and in some cases, even breathe and swallow

Spine. Image courtesy Pearson Scott Foresman/Wikimedia Commons

Spinal muscular atrophy (SMA) is a severe genetic condition that targets motor neurons in the central nervous system (CNS), resulting in progressive muscle atrophy, weakness, and paralysis. It is a group of genetic disorders in which a person cannot control the movement of their muscles due to a loss of nerve cells in the spinal cord and brain stem. A person with SMA may find it challenging to stand up, walk, control their head movements, and in some cases, even breathe and swallow. Some forms of SMA are present at birth, while others develop over time. Some have an impact on life expectancy.

SMA can be clinically divided into five subtypes. The most severe type is SMA type 0, appearbefore birth, can be fatal before or after birth within the first year of life. Type 1 SMA also called infantile-onset, is the most common type of SMA, accounting for 60% cases, which appears in infants and causes them to die or become dependent on a ventilator by the age of two. Children with SMA type 2 are sitters, while those with type 3 can walk on their own for a while before becoming wheelchair-bound. SMA type 4 develops in adults and causes later-life progressive weakness.

SMA is the most frequent cause of death in the infantile age group, occurring in one in 10,000 live births. However, the SMA carrier frequency was 1 in 38 in a recent Indian study. Children with SMA can currently receive supportive care in India that includes assisted ventilation, feeding, physiotherapy, orthotics, and spine stabilization.

What causes SMA?

SMA is caused by a very specific genetic mutation in a gene called theSMN1 gene. SMN is that protein that play a critical role in the survival of the nerve cells that control muscles. (SMN) protein keeps motor neurons healthy and functioning normally. The loss of motor neurons in the spinal cord caused by SMA patients, and insufficient levels of the SMN protein results in skeletal muscle weakness and wasting.

SMA patients gradually lose their ability to control their muscles movement and strength. The muscles closest to the torso and neck are frequently severely affected by the disease. Some SMA patients never sit, stand, or walk. Other signs of SMA include tongue fasciculation, a bell-shaped chest (caused by muscle weakness), weak cough, difficulty breathing , choking or trouble swallowing, weak sucking and labored breathing during feeding.

How is SMA diagnosed?

The diagnosis of spinal muscular atrophy depends on the type of SMA a person has and age of onset. The path to diagnosis for infants and children with more severe forms of SMA frequently starts when a parent or medical professional notices unusual muscle weakness (hypotonia). People with adult-onset SMA types, such as type 4, might begin the diagnosis process after observing minor symptoms like hand tremors.

Physical exam

A physical examination is required to identify the presence of symptoms like muscle weakness or a lack of reflexes in cases where a new-born is not screened for SMA at birth. A primary care physician or a neurologist could perform this.

Family medical history

As part of your or your childs physical examination, a thorough review of the patients family history is necessary to determine whether there have ever been any instances of neuromuscular disease in the family. If the physical examination and family history raise suspicion of SMA, genetic testing will likely be the next step.

Genetic testing

Through molecular genetic testing, which requires a blood sample, SMA is identified. A single gene is examined for mutations linked to a genetic disease in molecular genetic testing.

Importance of early diagnosis

A patient with SMA must first undergo a higher level of cognitive evaluation. The clinician should assess the patient for weakness before concentrating solely on SMA. A muscle biopsy could be the next step in the evaluation to more precisely distinguish between muscle weakness and nerve weakness. Finally, the clinician would probably identify this patients SMA based on the results of the combined muscle biopsy and electrode diagnostics.

If a diagnosis is made early, the individual has access to the tools and the resources that medical science has developed over the last number of years to assist optimal functioning.

The standard method for diagnosing SMA is molecular genetic testing. SMA should be given early consideration in any infant with weakness or hypotonia due to the effectiveness of molecular testing and high frequency of SMA in the hypotonic infant. All other infant causes of hypotonic weakness are included in the differential diagnosis of severe forms of SMA.

SMA is inherited in an autosomal recessive manner. Each pregnancy of a couple who have had a child with SMA has an approximately 25 per cent chance of producing an affected child. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the diagnosis of SMA has been confirmed by molecular genetic testing in an affected family member.

Currently, there are several SMA treatments that have received FDA approval including Risdiplam (Evrysdi), Onasemnogene abeparvovec-xioi (Zolgensma) and Nusinersen (Spinraza). These targeted treatments may prevent the development or slow the progression of some features of SMA.

The severity of the disease varies depending on the type of SMA, with more severe subtypes needing more aggressive treatment. Proactive care and treatment decision-making by the multidisciplinary team and family are of paramount importance.

The author is MBBS, DCH, MRCPCH, Fellowship Pediatric Genetics, Consultant Clinical Geneticist, Salem Genetics Centre. Views are personal.

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Spinal Muscular Atrophy: Causes and importance of early diagnosis for proactive management - Firstpost

Spinal Cord Stem Cells Comments Off on Spinal Muscular Atrophy: Causes and importance of early diagnosis for proactive management – Firstpost | September 11th, 2022

DUBLIN--(BUSINESS WIRE)--The "Induced Pluripotent Stem Cells Market - Growth, Trends, Covid-19 Impact, and Forecasts (2022 - 2027)" report has been added to ResearchAndMarkets.com's offering.

The Induced Pluripotent Stem Cells Market is projected to register a CAGR of 8.4% during the forecast period (2022 to 2027).

Companies Mentioned

Key Market Trends

The Drug Development Segment is Expected to Hold a Major Market Share in the Induced Pluripotent Stem Cells Market.

By application, the drug development segment holds the major segment in the induced pluripotent stem cell market. Various research studies focusing on drug development studies with induced pluripotent stem cells have been on the rise in recent years.

For instance, an article titled "Drug Development and the Use of Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Disease Modeling and Drug Toxicity Screening" published in the International Journal of Molecular Science in October 2020 discussed the broad use of iPSC derived cardiomyocytes for drug development in terms of adverse drug reactions, mechanisms of cardiotoxicity, and the need for efficient drug screening protocols.

Another article published in the Journal of Cells in December 2021 titled "Human Induced Pluripotent Stem Cell as a Disease Modeling and Drug Development Platform-A Cardiac Perspective" focused on methods to reprogram somatic cells into human induced pluripotent stem cells and the solutions to overcome the immaturity of the human induced pluripotent stem cells derived cardiomyocytes to mimic the structure and physiological properties of adult human cardiomyocytes to accurately model disease and test drug safety. Thus, this increase in the research of induced pluripotent stem cells for drug development and drug modeling is likely to propel the segment's growth over the study period.

Furthermore, as per an article titled "Advancements in Disease Modeling and Drug Discovery Using iPSC-Derived Hepatocyte-like Cells" published in the Multi-Disciplinary Publishing Institute journal of Cells in March 2022, preserved differentiation and physiological function, amenability to genetic manipulation via tools such as CRISPR/Cas9, and availability for high-throughput screening, make induced pluripotent stem cell systems increasingly attractive for both mechanistic studies of disease and the identification of novel therapeutics.

North America is Expected to Hold a Significant Share in the Market and Expected to do Same in the Forecast Period

The rise in the adoption of highly advanced technologies and systems in drug development, toxicity testing, and disease modeling coupled with the growing acceptance of stem cell therapies in the region are some of the major factors driving the market growth in North America.

The United States Food and Drug Administration in March 2022 discussed the development of strategies to improve cell therapy product characterization. The agency focused on the development of improved methods for testing stem cell products to ensure the safety and efficacy of such treatments when used as therapies.

Likewise, in March 2020, the Food and Drug Administration announced that ImStem drug IMS001, which uses AgeX's pluripotent stem cell technology, would be available for the treatment of multiple sclerosis. Similarly, REPROCELL introduced a customized iPSC generation service in December 2020, as well as a new B2C website to promote the "Personal iPS" service. This service prepares and stores an individual's iPSCs for future injury or disease regeneration treatment.

Thus, the increasing necessity for induced pluripotent stem cells coupled with increasing investment in the health care department is known to propel the growth of the market in this region.

Key Topics Covered:

1 INTRODUCTION

2 RESEARCH METHODOLOGY

3 EXECUTIVE SUMMARY

4 MARKET DYNAMICS

4.1 Market Overview

4.2 Market Drivers

4.2.1 Increase in Research and Development Activities in Stem Cells Therapies

4.2.2 Surge in Adoption of Personalized Medicine

4.3 Market Restraints

4.3.1 Lack of Awareness Regarding Stem Cell Therapies

4.3.2 High Cost of Treatment

4.4 Porter's Five Force Analysis

5 MARKET SEGMENTATION

5.1 By Derived Cell Type

5.2 Application

5.3 End User

5.4 Geography

6 COMPETITIVE LANDSCAPE

6.1 Company Profiles

7 MARKET OPPORTUNITIES AND FUTURE TRENDS

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

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Global Induced Pluripotent Stem Cells Market (2022 to 2027) - Growth, Trends, Covid-19 Impact and Forecasts - ResearchAndMarkets.com - Business Wire

IPS Cell Therapy Comments Off on Global Induced Pluripotent Stem Cells Market (2022 to 2027) – Growth, Trends, Covid-19 Impact and Forecasts – ResearchAndMarkets.com – Business Wire | September 11th, 2022

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Clinical translation of stem cell therapy for spinal cord injury still premature: results from a single-arm meta-analysis based on 62 clinical trials...

IPS Cell Therapy Comments Off on Clinical translation of stem cell therapy for spinal cord injury still premature: results from a single-arm meta-analysis based on 62 clinical trials… | September 11th, 2022