Doctors use stem cell transplants to treat patients with certain cancers or blood disorders. And donors, whose blood or bone marrow is used for the procedures, are typically young, for a variety of reasons.

But a pilot study released Wednesday raised the possibility that such donors are also passing along mutations in stem cells that could lead to health problems for some recipients.

The study found that nearly 45% of younger donors had mutations in the transplanted stem cells that could raise the risk of conditions that are sometimes seen in recipients, a higher rate than presumed. Researchers also reported that some of these mutations persisted and proliferated in the recipients bone marrow for at least a year.

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What remains unknown is whether those mutations are actually contributing to health problems for recipients.

The study was small, with just 25 donors included and was not large enough and did not last long enough to determine whether people who received cells with these mutations had worse outcomes after a transplant than recipients who got cells without those mutations. Dr. Todd Druley, the senior author of the paper, which was published in the journal Science Translational Medicine, emphasized that patients should continue to receive these stem cells to treat their leukemias or anemias when recommended.

What were trying to say is that now we can provide surveillance before, during, and after a bone marrow transplant so that if theres an increased risk for a particular outcome, treatment for that and surveillance for that can be instituted sooner, said Druley, a pediatric oncologist at Washington University in St. Louis.

Researchers not involved with the study praised its technical prowess, and said it was worth investigating further to see if the transplanted mutations did lead to worse outcomes for recipients projects that Druley and his colleagues have underway. But they agreed it should not yet change clinical practice.

Donors are already screened to make sure they have a clean bill of health and make for a good match for recipients, based on their immune systems. Experts said it would be unrealistic to screen every potential donor for the kinds of mutations Druley and his team found. Those mutations were infrequent, and it wasnt clear they posed health risks to recipients.

We know that younger donors are better than older donors. We know that the better the donor the better the outcomes. We dont know how these ultra-low level mutations affect outcomes at all, said Dr. Corey Cutler, the medical director of the adult stem cell transplantation program at Dana-Farber Cancer Institute.

Hematopoietic stem cells generate blood and immune cells. They are sometimes transplanted into patients with certain blood or immune disorders or cancers whose own cells have been wiped out by chemotherapy, essentially restocking the recipients with healthy cells.

But recipients of these transplants sometimes experience graft versus host disease (when the transplant attacks the recipients tissues), heart or immune conditions, or even secondary cancers. Some experts have suspected these conditions might be caused by mutations in donor stem cells, among other factors. Its in part why they favor younger donors, who are expected to have fewer mutations than older donors. (Donors from 18 to 44 account for 86% of transplants for unrelated patients. Relatives often make for better donors because they are more likely to be matched to recipients based on immune system molecules.)

Most of these mutations are probably benign. But its possible that other mutations not only pose a health risk, but also give their host cells a boost over other cells, helping them proliferate over time. That might mean someone who is 40 could have a bad mutation in one in 5,000 cells, but by the age of 50, it could be in one in 50 cells, Druley explained.

The challenge is detecting those mutations. Standard sequencing technology may pick up mutations if they appear in just a small percentage of cells, but for young donors, it would be like finding the few pebbles in a beach full of sand.

Next-generation sequencing is good if you want to find a mutation thats in 20% of cells youre looking at, or even 5%, Druley said. Were looking at mutations that are one in a thousand, or down to one in ten thousand.

For the new study, Druley and colleagues trained a more powerful tool they call error-corrected sequencing on the cells of the 25 donors, who ranged from 20 to 58 years old. (Fifty-eight would be considered older donors, but the median age of the donors in the study was 26.) They looked for mutations in 80 genes in particular, including genes that, when mutated, are associated with leukemia.

What they found: 11 donors had a collective 19 mutations that were not picked up by standard sequencing technology 16 of which were pathogenic, meaning disease causing.

The researchers also studied the recipients, finding that 14 of the 19 mutations had engrafted, or been taken up by the recipient and started to generate other cells, and were still there a year after the transplant. Thirteen of these mutations were pathogenic.

Researchers said it made sense that younger adults had these types of mutations, even if scientists hadnt previously been able to spot them.

Its known that mutations accumulate over time, said Dr. Ross Levine, a leukemia specialist at Memorial Sloan Kettering Cancer Center, who was not involved in the new study. The question has always been in other scenarios if you can detect these clones at earlier or in different contexts, and if they mean anything.

The new study was not set up to answer that last question.

Thats the next phase of this research, Druley said. Some of these mutations, if theyre going to have an effect, may not have an effect for many, many years. And we had a small population. So we didnt have enough numbers or enough time.

Outside researchers said that if these stem cell mutations do contribute to diseases once transferred to recipients, it might take so long or happen so infrequently that it would be difficult to study. Dana-Farbers Cutler said that, for example, cases of donor-derived leukemia when the recipient develops blood cancer after a transplant occur in less than 1% of transplants from unrelated donors.

If the mutations do increase the likelihood of complications in recipients, then why arent they posing a problem for the donors themselves? That might also be tied to the prevalence of these mutations, the researchers said.

In donors, these mutations might appear in, say, 1% of cells, and there is competition among cells of all different types of genetic variants to multiply. Plus, donors have healthy immune systems that can help suppress bad actors.

But if cells with these mutations make their way into recipients who have had their own cells blasted away with chemotherapy, its a new race. The mutations might give them some advantage to multiply faster than other cells that were transplanted. And as the percentage of cells with these mutations rises, they might be more likely to cause disease.

When you have these mutations in a host, it may take decades for them to expand to the point of causing issues, Levine said. In a recipient, however, its almost like youve reset the playing field.

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Study: Mutations in stem cells of young donors can be passed to recipients - STAT

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Research findings show that rare mutations from donor stem cells can be passed onto patients who receive them, potentially causing health concerns.

Researchers from Washington University School of Medicine in St. Louis discovered this while analyzing bone marrow samples from 25 adult patients with acute myeloid leukemia (AML).

Heart damage, graft-versus-host disease and, potentially, new leukemias, are the risks associated with these mutations.

There have been suspicions that genetic errors in donor stem cells may be causing problems in cancer patients, but until now we didnt have a way to identify them because they are so rare, senior author Dr. Todd E. Druley, an associate professor of pediatrics, said in a news release. This study raises concerns that even young, healthy donors blood stem cells may have harmful mutations and provides strong evidence that we need to explore the potential effects of these mutations further.

The harmful mutations were found in surprisingly young donors, explained the researchers. Healthy donors ranged in age from 20 to 58, with an average age of 26 years old. Interestingly, the mutations, because they are so rare, were not detected using usual genome sequencing techniques.

In the study, the researchers sequenced 80 genes that are associated with AML using a technique called error-corrected sequencing. They found at least one harmful genetic mutation in 11 of the 25 donors. Eighty-four percent of the mutations identified in the donor samples were potentially harmful and 100% of the harmful mutations were found in the recipients the most common mutation seen is a gene associated with heart disease.

We didnt expect this many young, healthy donors to have these types of mutations, Druley said. We also didnt expect 100% of the harmful mutations to be engrafted into the recipients. That was striking.

These harmful mutations persisted over time, and many increased in frequency, explained the researchers.

In addition, 75% of patients who received at least one harmful mutation developed chronic graft-versus-host disease. In patients who didnt receive a mutation, 50% developed the condition. Graft-versus-host disease either acute or chronic, can occur in patients who receive an allogeneic transplant, which consists of donor stems cells versus a patients own stem cells.

The researchers plan to examine the mutations in a larger study to answer the questions that this study revealed.

Transplant physicians tend to seek younger donors because we assume this will lead to fewer complications co-author Dr. Sima T. Bhatt, an assistant professor of pediatrics who treats pediatric patients with blood cancers at Siteman Kids at St. Louis Childrens Hospital and Washington University School of Medicine, said in a news release. But we now see evidence that even young and healthy donors can have mutations that will have consequences for our patients. We need to understand what those consequences are if we are to find ways to modify them.

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Mutations in Donor Stem Cells Could Harm the Health of Patients with Cancer, Study Finds - Curetoday.com

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In November 2018, Chinese biophysics researcher He Jiankuimade a historic announcement.

Two twin girls nicknamed Lulu and Nana had become the worlds first genetically modified human beings.

Using a gene-editing technology known as CRISPR, He had manipulated the DNA of the embryos that would become the girls in an effort to make them immune to the HIV virus.

What first seemed like a historic triumph of science, however, quickly became one of the most infamous scandals in medical history.

The researcher was swiftly fired from his university, put under police investigation, and denounced by experts around the world who said he jumped the gun and carried out an experiment that was unsafe and unethical.

In December, He was sentenced to three years in prison for illegally carrying out human embryo gene-editing intended for reproduction. Its unclear whether the experiment caused any genetic damage to Lulu and Nana or if they are even resistant to the HIV virus.

Kiran Musunuru, one of the worlds foremost genetics researchers, was the first expert to publically condemn Hes experiment.

Nonetheless, Musunuru says the birth of the Chinese twins marks the beginning of a new human era, the possibilities of which are boundless.

Potential future implications of gene-editing technology range from preventing genetic diseases to producing designer babies with custom traits to creating superhumans and controlling our own evolution.

With the release of his new book, The CRISPR Generation: The story of the Worls First Gene-Edited Babies, The Globe Posts Bryan Bowmanspoke to Musunuru about where this technology could go from here and what it could mean for the future of humanity.

The following interview is lightly condensed and edited for length and clarity.

Bowman: Could you explain what CRISPR is broadly and how that technology evolved to where it is today?

Musunuru: CRISPR is one type of gene-editing tool. Gene editing is a technology that allows us to make changes to genes in the DNA and in the cells in the body. If were talking about human beings, typically were talking about changes that are related to health or disease.

There are several types of gene editing tools, but CRISPR is by far the most popular one. CRISPR is interesting because it wasnt invented. It actually exists naturally in all sorts of bacteria. It evolved as a sort of an immune system that can fight off viral infections. Just like we can get viral infections, it turns out bacteria can get viral infections as well. And so bacteria created a system by which they can fight off viruses. So thats where CRISPR came from.

Over the past couple of decades, a variety of very talented scientists identified it, discovered it in bacteria, and then were able to adapt it into a gene-editing tool that can now be used in human cells.

What we can do with CRISPR is either turn off genes and thats easier to do or we can make more precise changes to genes such as correcting a mutation that causes disease.

Bowman: Last year, there was the famous or infamous case where Dr. He Jiankui in China covertly created the first gene-edited babies. And I understand that you were the first expert to publicly condemn the experiment. What exactly did Dr. He do and why did you feel it was so unethical?

Musunuru: What he was trying to do was use CRISPR to turn off a gene called CCR5. By turning off this gene, he was hoping to make the babies that were born resistant to HIV infection, HIV being the virus that causes AIDS.

There are many people who are naturally born with this chain turned off and theyre resistant to HIV. So the rationale was, well, Im going to try to create babies who have the same trait.

What he did was problematic for two reasons. One, it was, to put it lightly, a scientific disaster. Everything you worry about going badly with CRISPR actually did happen. Any technology has a potential for a lot of good with the potential for bad. I compare it to fire. It can be very useful. But if youre not careful, it can cause wildfires and a lot of damage and hurt a lot of people. Its the same with CRISPR. It can do a lot of good. It can help patients who have bad diseases. But if youre irresponsible with it, it could actually cause unintended genetic damage.

Its not clear whether these kids that were born they were twin girls nicknamed Lulu and Nana its not clear whether theyre actually protected against HIV infection. Its not clear whether they might have suffered some genetic damage that might have health consequences for them. Its not clear whether the genetic damage if it did occur could get passed down to their children and affect future generations.

So scientifically, there are a lot of problems with it. The work was very premature. I would say that if we were ever going to do this in a reasonable, rational, safe way, were years away from doing it. But he went ahead and just did it anyway. You can call him a rogue scientist, as clich as it is. And he did it in conditions of secrecy. There was essentially no oversight. And potentially these twins and future generations might suffer the consequences.

The other problem is a problem of ethics. The way in which he did it basically violated every principle of ethical medical research in the textbook. Basically, everything that you could do wrong, he did it wrong.

Whenever we do an experimental procedure, we hope that the benefits greatly outweigh the risks. What he was trying to do was protect these kids from HIV. But the truth is, they were in no particular danger of getting HIV compared to the average person. In China, the prevalence of HIV is about 0.1 percent. So there wasnt really much for them to gain. Even if they did somehow during their lifetime get the HIV infection, we have good treatments to prevent it from proceeding to full-blown AIDS.

So what was the benefit of doing this procedure? You have to balance that against the harms. And the genetic damage thats possible that raises risks of things like cancer and heart disease and other diseases. When you have those risks and very little benefit, then its just not a favorable ratio. And thats intrinsically unethical.

Bowman: Seeing as you said that were years away from doing something like this in a more responsible and ethical way, what are the greatest challenges to getting to a point where parents will have the option to go forth with a gene-editing procedure that might prevent their children from suffering from some kind of genetic disease?

Musunuru: There are really two aspects to this. One is a scientific or medical aspect. Can we get to a place where gene-editing of embryos is well-controlled? Where we know that what were doing is truly safe and appropriate from that perspective?

The second issue is really a decision more for broader society. Is this something that we should be doing, something we want to be doing? This is less about the science and more about ethics and morality and legality and religious values and all sorts of other things. Reasonable people can disagree on whats appropriate and whats not appropriate.What complicates things here is that its not really an all or nothing decision. There are different scenarios where you could see parents using gene-editing on behalf of their unborn children.

I like to break it down is three scenarios. The first scenario is with parents who have medical issues that make it so that theres no way they can have natural biological children or healthy babies if they both have a bad disease and theyre going to pass it on to all of their kids unless you do something like editing. These are unusual situations, but they do exist.

The second scenario is one where parents might want to quite understandably reduce the risk of their child having some serious illness at some point in their lifetime. Im talking about things that are fairly common, like Alzheimers disease or breast cancer or heart disease or whatnot. Theres no guarantee that the editing will eliminate that risk. But you can see how parents might want to stack the odds in their kids favor. Its still medical, but its not perhaps as severe a situation with a kid whos definitely going to get the disease unless you do something.

The third scenario would be cases in which parents want to make changes that are not really medical but are more of what we would think of as enhancements. These could be cosmetic changes like hair color, eye color, things like that.

But it could potentially be much more serious things like intelligence or athletic ability or musical talent. Now, to be fair, thats theoretical. I dont think we are anywhere near knowing enough about how genes influence these things to be able to do it anytime soon. You might actually have to change hundreds of genes in order to make those changes. But you can imagine how certain parents might want to do that, might want to advance their children in the ways that they feel personally are desirable.

Bowman: Can gene editing only be performed on embryos or is it possible to edit genes in later stages of pregnancy or even post-birth?

Musunuru: Theres actually a lot of exciting work going on using gene editing to help patients, whether its adults or children. Right now its been focused mostly on adults who have terrible diseases and its really being used as a treatment to alleviate their suffering or potentially cure the diseases.

Just recently, we got the exciting news that two patients one in the U.S. and one in Europe were participating in a clinical trial. They each had a severe blood disorder. One of them had sickle cell disease. The other had a disease called beta-thalassemia. Earlier this year, they got a CRISPR-based treatment. And whats very exciting is that it looks like not only have their conditions improved significantly, it looks like they might actually be cured.

If that bears out, it would really be historic because these are diseases that affect millions of people around the world and were previously incurable. This treatment is also being explored for things ranging from cancer to liver disease to heart disease.

So theres enormous potential for benefit for living people who have serious diseases. But its a very different situation than editing embryos because youre talking about a person who is in front of you. We are trying to alleviate their suffering. That patient has the ability to freely give consent to the procedure, to weigh the benefits and risks and come up with a decision.

Bowman: How does that work? Is it some kind of cell transplant where the new cells then replicate throughout the rest of the body?

Musunuru: Yeah. It depends on the situation. I mentioned those two patients with the blood disorders. The way it worked there was the medical team used bone marrow stem cells. They basically took bone marrow as if they were going to do a transplant and then edited blood stem cells in a dish outside of the body to fix the genetic problem. And then they took those edited stem cells and put them back into the same patient. Those cells start making the blood cells that are now corrected or repaired. And by doing that, to cure the disease.

Another potential implementation is I work on heart disease. And what wed like to be able to do is turn off cholesterol genes in the liver. So what I envision is that a patient with heart disease would get a single treatment and it would deliver CRISPR into the liver and just the liver. It would turn off genes that produce cholesterol in the liver. The effect of that is permanent reduction of cholesterol levels and lifelong protection against heart disease.

This actually works really well in mice. Ive been working on this in my own laboratory for six, almost seven years now experimenting with it in monkeys. And if looks like it works and Im pretty confident that it will work we could be looking at clinical trials in a few years where were taking patients who have really bad heart disease or a very high risk for heart disease and actually giving them the single treatment within their own bodies that would turn off these cholesterol genes.

Bowman: In terms of more cosmetic applications, theres this popular idea that designer babies will be a reality at some point in the future. But how feasible would it be to use gene-editing for something very basic like choosing eye color or hair color? Are there many genes involved in determining traits like that? Are we close to being able to do that if we choose to?

Musunuru: Well, eye color, hair color, those actually turned out to be fairly simple. Theres only a small number of genes that control those. So in theory, if you wanted to do it, it wouldnt be that difficult.

Personally, my point of view is thats a trivial thing. Like why would you go through all that trouble? Do I care if your kid has blue eyes versus green eyes versus brown eyes? Maybe some parents feel that thats very important. So I think simple things like hair color, like eye color, it could be done fairly readily. I just dont see it as serious enough to warrant doing it.

The more complex things like intelligence, gosh, thats going to be so challenging. I mean, intelligence is just such a complex phenomenon. Theres some genetics involved in it, but there are so many other factors that come into that like upbringing and environment. Were not even getting close to an understanding of how someones intelligence comes about, to be perfectly honest about it.

I will point out that even though some of these things are simpler, in general, the vast majority of people are very, very uncomfortable with the idea of using gene editing of embryos for enhancements.

And I think this reflects a couple of things. I think this reflects the fact that people are more sympathetic if something like this is being used for medical purposes and much less comfortable if its being done to give a child an advantage in a way thats not medical.

It brings to mind the recent scandal where wealthy parents were trying to get their kids into good colleges by actively bribing admissions officers, faking test scores, fabricating resums. That kind of thing makes people very uncomfortable that certain people, particularly wealthy people, might try to use this technology to an extreme to advantage their children.

Theres an economic aspect to that. Wealthy parents might have better access to this technology than those who are not as wealthy. And what does that mean? If wealthy parents are somehow able to make designer babies who somehow are advantaged and other people are not, does that exacerbate socio-economic inequalities in our society?

So I think there are a few reasons why people are uncomfortable with the idea of enhancement, whereas on the whole, the majority seem to be at least somewhat open to the idea that there might be good medical uses.

Bowman: Im really happy that you brought up that socio-economic inequality aspect because I was going to ask you about that. But if we table those concerns for a moment and go way out there, theres this notion you write about that we could ultimately, theoretically, control our own evolution.

Ive heard it suggested that it could be theoretically possible to incorporate traits from other organisms that could be advantageous into our own DNA and essentially enter a new post-human stage of evolution. Is that total science fiction or do you think were entering a period where that is increasingly possible?

Musunuru:Well, with the way things are going with this technology. I mean, weve taken a step towards that. But there are many, many, many, many steps that would need to be taken to actually get to that point. But I think youre right. You see the path. We have the technology. Then its a question of perfecting the technology. A question of learning more about what genes from other species might be advantageous.

The cats out of the bag. The technology is here. Whether its five years from now or 10 years from now or 50 years from now or 100 years from now, these sorts of things will inevitably start to happen. And Im not sure theres much that those who would like to not see that happen will be able to do to stop it in the long run.

China Jails Scientist Who Gene-Edited Babies

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Controlling Our Own Evolution: What is the Future of Gene-Editing? - The Globe Post

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Stem Cell Assay Market: Snapshot

Stem cell assay refers to the procedure of measuring the potency of antineoplastic drugs, on the basis of their capability of retarding the growth of human tumor cells. The assay consists of qualitative or quantitative analysis or testing of affected tissues and tumors, wherein their toxicity, impurity, and other aspects are studied.

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With the growing number of successful stem cell therapy treatment cases, the global market for stem cell assays will gain substantial momentum. A number of research and development projects are lending a hand to the growth of the market. For instance, the University of Washingtons Institute for Stem Cell and Regenerative Medicine (ISCRM) has attempted to manipulate stem cells to heal eye, kidney, and heart injuries. A number of diseases such as Alzheimers, spinal cord injury, Parkinsons, diabetes, stroke, retinal disease, cancer, rheumatoid arthritis, and neurological diseases can be successfully treated via stem cell therapy. Therefore, stem cell assays will exhibit growing demand.

Another key development in the stem cell assay market is the development of innovative stem cell therapies. In April 2017, for instance, the first participant in an innovative clinical trial at the University of Wisconsin School of Medicine and Public Health was successfully treated with stem cell therapy. CardiAMP, the investigational therapy, has been designed to direct a large dose of the patients own bone-marrow cells to the point of cardiac injury, stimulating the natural healing response of the body.

Newer areas of application in medicine are being explored constantly. Consequently, stem cell assays are likely to play a key role in the formulation of treatments of a number of diseases.

Global Stem Cell Assay Market: Overview

The increasing investment in research and development of novel therapeutics owing to the rising incidence of chronic diseases has led to immense growth in the global stem cell assay market. In the next couple of years, the market is expected to spawn into a multi-billion dollar industry as healthcare sector and governments around the world increase their research spending.

The report analyzes the prevalent opportunities for the markets growth and those that companies should capitalize in the near future to strengthen their position in the market. It presents insights into the growth drivers and lists down the major restraints. Additionally, the report gauges the effect of Porters five forces on the overall stem cell assay market.

Global Stem Cell Assay Market: Key Market Segments

For the purpose of the study, the report segments the global stem cell assay market based on various parameters. For instance, in terms of assay type, the market can be segmented into isolation and purification, viability, cell identification, differentiation, proliferation, apoptosis, and function. By kit, the market can be bifurcated into human embryonic stem cell kits and adult stem cell kits. Based on instruments, flow cytometer, cell imaging systems, automated cell counter, and micro electrode arrays could be the key market segments.

In terms of application, the market can be segmented into drug discovery and development, clinical research, and regenerative medicine and therapy. The growth witnessed across the aforementioned application segments will be influenced by the increasing incidence of chronic ailments which will translate into the rising demand for regenerative medicines. Finally, based on end users, research institutes and industry research constitute the key market segments.

The report includes a detailed assessment of the various factors influencing the markets expansion across its key segments. The ones holding the most lucrative prospects are analyzed, and the factors restraining its trajectory across key segments are also discussed at length.

Global Stem Cell Assay Market: Regional Analysis

Regionally, the market is expected to witness heightened demand in the developed countries across Europe and North America. The increasing incidence of chronic ailments and the subsequently expanding patient population are the chief drivers of the stem cell assay market in North America. Besides this, the market is also expected to witness lucrative opportunities in Asia Pacific and Rest of the World.

Global Stem Cell Assay Market: Vendor Landscape

A major inclusion in the report is the detailed assessment of the markets vendor landscape. For the purpose of the study the report therefore profiles some of the leading players having influence on the overall market dynamics. It also conducts SWOT analysis to study the strengths and weaknesses of the companies profiled and identify threats and opportunities that these enterprises are forecast to witness over the course of the reports forecast period.

Some of the most prominent enterprises operating in the global stem cell assay market are Bio-Rad Laboratories, Inc (U.S.), Thermo Fisher Scientific Inc. (U.S.), GE Healthcare (U.K.), Hemogenix Inc. (U.S.), Promega Corporation (U.S.), Bio-Techne Corporation (U.S.), Merck KGaA (Germany), STEMCELL Technologies Inc. (CA), Cell Biolabs, Inc. (U.S.), and Cellular Dynamics International, Inc. (U.S.).

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Stem Cell Assay Market Predicted to Accelerate the Growth by 2017-2025 Dagoretti News - Dagoretti News

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The first squeeze of my left thumb is gentle, almost reassuring. I rate it as 0 out of 100 on the pain scale.

But as a technician ramps up pressure on the custom-made thumb-squeezing device, it becomes less pleasant. I give ratings of 2, 6 then 36. A few squeezes later, Im at 79.

At 84, Im glad the test is over as I put my tender thumb to my lips.

Ive offered myself up for a pain study at the University of Michigan, in a long, low-slung building northeast of the universitys main campus in Ann Arbor. As the day wears on, Ill undergo needle pokes, leg squeezes and an MRI scan all part of a grand bid to better understand the root cause of an individuals pain, and point to the best solutions.

Its an understanding thats sorely needed. Lucky for me, Im just a control in this experiment, and I can cry for mercy whenever I want. Thats not the case for the multitudes of people 50 million in the US alone who have ongoing, chronic pain, for whom the medical pause buttons are far from adequate.

The thumb pressure test, in which participants rate their pain level on a scale from 0 to 100 as their thumbs are subjected to increasing pressure, is one of several ways that clinicians and researchers can evaluate a persons pain responses. Since peoples thresholds to pain in tests like this vary according to pain syndrome, such tests can help with diagnosis.

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Our treatments for chronic pain are very bad, says Richard E. Harris, a neuroscientist at the University of Michigans Chronic Pain and Fatigue Research Center and a co-researcher on the study, which should ultimately help to improve diagnoses and therapies. Today, doctors mostly define pain by where it is: the abdomen, the lower back, the joints. Then they offer up treatments, usually anti-inflammatories or opioids, that too often do nothing to the cells and molecules causing a person to hurt. A recent analysis in the Journal of the American Medical Association found that opioids reduced pain by an average of less than one point on a 10-point scale, across a variety of chronic conditions.

As part of the precision medicine movement and thanks to modern brain-imaging technology, scientists are starting to puzzle out the different types of pain: what causes them, how to diagnose them and how to prescribe treatments to match. Its an area that is far from settled. As recently as 2017, the International Association for the Study of Pain defined a new pain type, called nociplastic. Its characterized by the absence of any nerve or tissue damage in the parts that hurt.

Dan Clauw, director of the Michigan pain center, is passionate about helping people with this kind of long-misunderstood pain, which could underpin chronic conditions, such as fibromyalgia, that afflict millions. His blue eyes flash behind spectacles as he describes crisscrossing the globe to educate other physicians about nociplastic pain. Hes wearing a navy blazer and slacks when we meet for lunch between my testing sessions, because hes just returned from giving a presentation about marijuana and pain. He jokes that his colleagues wont recognize him out of his usual jeans.

Imaging the brain, along with doing prodding and poking tests of the type I endured, is beginning to point to signatures that explain the problem and suggest solutions. Eventually, this knowledge will help scientists to develop more targeted therapies, so doctors can treat patients better.

In broad strokes, pain falls into three categories: nociceptive, neuropathic and nociplastic. (Noci- is from the Latin for to do harm.)

Nociceptive pain results from inflammation or direct damage to tissues. When that torture device squeezes my thumb, for example, pain-sensing nerves notice the pressure and spring into action. They transmit messages to my spinal cord, which sends them on to my brain, telling me Ouch!

This kind of discomfort is often short-lived; mine dissipates after Ive sucked on my thumb for a few moments. Nociceptive pain can also be chronic, though for example in osteoarthritis, where the cartilage in joints wears away and causes stretching of tendons and ligaments, or through the ongoing inflammation of rheumatoid arthritis.

Neuropathic pain, in contrast, happens when the pain-sensing nerves themselves are damaged or irritated, so that they send inappropriate Ow! signals to the brain. It typically results from some injury or disease, such as diabetes or shingles. It can also happen when a nerve is pinched, as in the case of carpal tunnel syndrome, when a nerve in the wrist gets squeezed. Its often long-lasting, unless the damage is repaired.

And nociplastic, the newly named type, results from no obvious inflammation or injury. Rather, its as if the volume knob for pain is turned up way too high, not at the pain site itself but further afield. Nociplastic pain seems to arise in parts of the central nervous system the brain or spinal cord that receive, transmit, or process those Ouch! signals. These nerves misfire, creating a sensation of pain even though nothing may be wrong. The location of the problem, the central nervous system, is why Clauw prefers to call it central sensitization. The classic example is fibromyalgia, which causes pain that seems to stem from muscles, tendons and joints, despite the real problems lying in the brain or spinal cord.

Scientists understanding of pain continues to evolve and so do the various terms used to describe it. Ideally, definitions are standardized and reflect the biology underpinning the pain, but the lack of straightforward tests for parsing types of pain makes defining it a challenge. Nociceptive pain involves pain-sensing nerves called nociceptors, which also can be involved in neuropathic pain. A third pain type is believed to arise wholly in the central nervous system. But there can be overlap: Nociceptive and neuropathic pain can, over time, lead to central nervous system-generated pain.

Complicating the picture, a person might have more than one type of pain going on at the same time. In 2012, the journal Pain published a case report of a person with burning, prickling pain on both sides of the body. Treatment with pregabalin, an epilepsy medication that can also address neuropathic pain and central sensitization, relieved pain on the right side of the body, but not the left.

All this pain classifying is more than an academic exercise: It should help guide how to treat people. For example, consider a patient with knee pain. If the issue is nociceptive, anti-inflammatories or knee surgery should help. But if the problem is central, those treatments probably wont make much difference. A better bet would be medications that can directly influence the misfiring central nervous system. Some antidepressants, for example, act on the brains chemical messengers neurotransmitters that are involved in pain, altering their signaling to quell the Ouch message.

Nondrug treatments such as acupuncture and cognitive behavioral therapy also may help because they influence how the brain perceives pain. Acupuncture boosts availability of brain receptors that respond to the bodys natural painkillers. A recent analysis in JAMA Internal Medicine of more than 6,000 people taking opioids found that treatments such as meditation, hypnosis and cognitive behavioral therapy reduced pain and diminished the drug doses needed to control it.

Though the term nociplastic is new, Clifford Woolf, a neurobiologist at Boston Childrens Hospital and Harvard Medical School, first proposed the concept in 1983. Yet the idea has been slow to catch on. In the 1990s, when Clauw began studying fibromyalgia, it was a disease so vague, so puzzling, that some physicians simply denied its existence.

Today, fibromyalgia is more likely to be accepted as a real condition. But many doctors still dont appreciate how centralized problems might underlie pain even when the symptoms look nociceptive or neuropathic, Clauw says. The distinctions between pain types are not clean: If left untreated, nociceptive pain may sensitize the nervous system, turning a temporary problem into chronic, nociplastic pain, for example. Clauw and his Michigan colleagues believe that central sensitization shows up in myriad conditions, from irritable bowel syndrome to chronic pelvic pain to dry eye disease. And in the study Ive signed up for, they want to clarify how often this happens and how doctors might detect it in patients who show up begging for pain relief.

To that end, the team has enrolled people with three different pain disorders that seem, on the surface, to be nociceptive or neuropathic. The scientists will test their pain before and after standard treatments. If the pain is in fact central, the treatments shouldnt work a disappointment for the participants, but one that might eventually lead to better understanding and treatment for them and others like them.

Two categories of subjects have what looks like nociceptive pain: those with osteoarthritis of the hip, who will receive a hip replacement, and those with inflammatory rheumatoid arthritis, who will be treated with modern medications. A third group, people with carpal tunnel syndrome, represent neuropathic pain and will get surgery to receive the pressure on the nerve.

But if Clauw and his crew are right, then some of these people will really be suffering from central sensitization, instead of or in addition to the nociceptive or neuropathic problem. Two control groups will help tease that out: People with fibromyalgia will show the researchers what pure central sensitization looks like, and those like me, with no chronic pain, will represent the non-central state.

The primary way that physicians measure pain today is to ask someone how much theyre hurting. Identification of biomarkers from, for example, brain imaging or blood tests could provide more objective measures of pain that would offer benefits in a variety of settings.

Once all the data are in, the researchers hope that pain features shared by the people with fibromyalgia and the others whose treatments dont work will reveal a potential signature for central sensitization.

The challenge is that theres no simple blood test or X-ray that will distinguish one type of pain from another. Theres no single measure that, by itself, will represent pain, says Woolf, author of a paper in the Annual Review of Neuroscience about pain caused by problems in the sensory machinery. We need a composite.

To build that composite, scientists must resort to a variety of indirect measures, including responses to the pokes and prods being inflicted on me and other subjects.

This particular piece of the picture, called quantitative sensory testing or QST, measures the threshold at which a person can feel a given sensation such as pressure, heat or cold and when that sensation becomes painful. This can reveal how a persons nervous system deals with pain, and how that system might be off-kilter. Specific defects in nerves lead to specific changes in pain responses, helping scientists to distinguish one pain type from another.

Its simple, but revealing. For example, in the case of the thumb-press test, a person with fibromyalgia would probably start to feel pain at around four pounds of pressure. Clauw, who has no chronic pain of any stripe and is relatively pain-insensitive, says that he can handle up to about 18 pounds of pressure before it becomes uncomfortable. The average person would probably start to feel bothered at around eight pounds.

Or take a test where Im poked in the forearm with a needle. The device retracts into the handle like a Hollywood special-effects knife, so it doesnt pierce my skin, but it doesnt feel great I rate it a 7 out of 100. Then I get 10 pokes in quick succession. That hurts more, at 32. This is a normal response, but if I had central sensitization, I would likely have found the 10-poke series much more painful.

In addition to sorting out nociceptive or neuropathic from centralized pain, QST also seems able to reveal subtypes. In research published in 2017, three European consortia performed QST on 900 people with diverse pain conditions, all considered to be neuropathic. The testing separated the subjects into three clusters, and the study authors predicted that each would be suited to different treatments.

Better-defined markers for different types of pain could radically improve pain management. As shown, it would allow patients to be sorted into clinical trials that would reveal the best treatments for each pain subtype. Results of those trials would help physicians treat individual patients more effectively.

The first cluster was characterized by deficits in sensation to touch, heat, or pokes that would normally be painful. This suggests that central sensitization might be behind the pain in some of these people, says study coauthor Nadine Attal, a pain specialist at the Assistance Publique-Hpitaux de Paris. Opioids, antiepileptics or antidepressants (used for their effects on pain nerves, not mood) might help, because they act in the brain.

The second group was defined by extreme sensitivity to hot and cold like skin when its sunburned, which puts pain-sensing nerves on high alert. For this kind of neuropathic pain, local, numbing medications such as lidocaine, Botox or capsaicin (a therapeutic substance from hot peppers) might be the right choice.

People in the third group were particularly sensitive to pressure and pinpricks, and its members often reported pain akin to burning or electrical shock. This was a more complex group, Attal says; she thinks topical medications or antiepileptics might help. But now that researchers have the categories better defined, they can directly test medications to find what truly works best for each.

Looking at the brain in pain also can help scientists distinguish pain types, although the answers arent clear-cut. Theres no one, lone spot where pain lights up the brain, says Sean Mackey, chief of the division of pain medicine at Stanford University in California. Rather, the pain response is distributed across a circuit that encompasses several brain areas.

In the afternoon of my day as a pain-study subject, Im led to the universitys North Campus for an MRI. The technician slides me into a gray, General Electric-branded, upright donut about the size of a golf cart. The outside is festooned with frolicsome animal stickers (many subjects from other studies are children), but these do nothing to allay the discomfort of lying perfectly still with my head in a vise for an hour and a half.

As I lie there, listening to the scanners inharmonious beeps, rumbles and alien-laser-gun sounds, Im not thinking of anything in particular. Nonetheless, certain parts of my brain tend to draw blood at the same time, suggesting that theyre acting in sync. These are called networks.

Roughly half of people with rheumatoid arthritis experience pain even when using medications that control the inflammation. MRI scans of some of these patients reveal amped up connectivity between two brain regions, the default mode network and insula. This brain connectivity also has been found in people with fibromyalgia, a chronic pain condition with roots in the central nervous system. The discovery suggests that rather than inflammation alone, a dysfunctional central nervous system can also play a role in the pain of rheumatoid arthritis.

CREDIT: IMAGE ACQUIRED AND GENERATED FROM THE CHRONIC PAIN AND FATIGUE CENTER WITH ASSISTANCE FROM THE FMRI LABORATORY AT THE UNIVERSITY OF MICHIGAN

One that Harris and colleagues are particularly interested in is called the default mode network. It turns on when Im at rest and my mind wanders to topics involving myself: what I had for breakfast, perhaps, or what Im planning for tonight once my day of pain is over.

Another network theyre watching is the salience network, which lights up when a person notices a new sensation say, the squeezing of their thumb to determine which sensations are worth responding to. It includes the insula, a pyramid-shaped bit of brain that Mackey and others have linked to pain.

Normally, the insula and the default mode network are unlikely to act at the same time. But Harris and colleagues discovered that in people with fibromyalgia, they were much more likely to flash in synchrony.

That makes sense, says Rob Edwards, a pain psychologist at Harvard Medical School and Brigham and Womens Hospital in Boston. For someone living with chronic pain, the pain can become a core part of their identity. The salience-related threat intrudes on, and even takes over, the way that you think about yourself, he says.

It may be possible to undo that intrusion, though. Edwards is currently testing cognitive behavioral therapy, or CBT, in people with fibromyalgia. In no way is he suggesting that their pain, or any pain, is imaginary, but therapy can help people deal with pain better and even reduce it. Its all about enforcing a sense of control and mastery, says Bob Kerns, a pain psychologist at Yale University in New Haven, Connecticut, who coauthored a paper in the Annual Review of Clinical Psychology on psychological treatment for chronic pain.

In the study so far, CBT seems to be disentangling the salience and default mode networks in some people with fibromyalgia. Edwards predicts those people will also experience pain relief.

Being able to forecast who will benefit from a given treatment could make a huge difference not just for individual patients, but also in clinical trials for new pain-relief drugs. If scientists test a pain drug on 100 people, but only a fraction of those subjects actually have the pain mechanism the drug can treat, the medicine will look like a flop even if its a superstar for a particular subset of patients. This has almost certainly happened in past trials, Woolf says.

Mackey envisions a future in which pain patients can be tested for the underlying problem, perhaps with the same kinds of tests I underwent at the University of Michigan, plus many more assessments. For example, scientists are analyzing nerve endings in small skin samples from pain patients, and others aim to tease out the role of genetics in chronic pain. Simple questionnaires can also help to identify pain types, all with this goal of prescribing medications tailored for a persons specific flavor of misery.

Medicine isnt quite there yet in fact, only 10 years ago Mackey would have called that scenario science fiction. Stay tuned, he says, because its no longer science fiction. . . . Were going to get there.

As required by the University of Michigan Institutional Review Board, Amber Dance was compensated $275 for her participation in the study at the Chronic Pain and Fatigue Research Center. She donated that amount to the American Chronic Pain Association.

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The unexpected diversity of pain - Knowable Magazine

Spinal Cord Stem Cells Comments Off on The unexpected diversity of pain – Knowable Magazine | January 17th, 2020

Researchers have developed cytochalasin B-induced membrane vesicles which they suggest could be a new form of cell-free therapy in regenerative medicine.

Work on extracellular microvesicles (ECMVs) derived from human mesenchymal stem cells (MSCs) has revealed a potential new form of cell-free therapy.

ECMVs are microstructures surrounded by a cytoplasm membrane; they have proven to be a prospective therapeutic tool in regenerative medicine due to their biocompatibility, miniature size, safety and regenerative properties. These can be used to circumvent the limitations of existing cell therapies without losing any effectiveness.

Cell therapies are grafts or implants of living tissue, such as bone marrow transplants, used to replace and regenerate damaged organ tissue. They currently have limited applications, as they work differently dependent on conditions and the environment they are placed into. They can also be rejected by the immune system.

A study at Kazan Federal University, Russia, has investigated cytochalasin B-induced membrane vesicles (CIMVs) which are also derived from MSCs and are very similar to natural ECMVs.

Proteome analysis of human MSCs and CIMVs-MSCs. Venn diagram of identified proteins MSCs and CIMVs-MSCs (A). Distribution of the identified proteins in organelles, percent of unique identified proteins (B) (credit: Kazan Federal University).

The scientists studied and characterised the biological activity of MSC-derived CIMVs. A number of biologically active molecules were found in CIMVs, such as growth factors, cytokines and chemokines; their immunophenotype was also classified.They also found that CIMVs could stimulate angiogenesis in the same way as stem cells.

The team came to the conclusion that human CIMVs-MSCs can be used for cell-free therapy of degenerative diseases. Induction of therapeutic angiogenesis is necessary for the treatment of ischemic tissue damage (eg, ischemic heart disease, hind limb ischemia, diabetic angiopathies and trophic ulcers) and neurodegenerative diseases (eg, multiple sclerosis and Alzheimers disease), as well as therapies for damage of peripheral nerves and spinal cord injury.

The group say they are continuing to research the therapeutic potential for artificial microvesicles for autoimmune diseases.

The study was published in Cells.

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Novel form of cell-free therapy revealed by researchers - Drug Target Review

Bone Marrow Stem Cells Comments Off on Novel form of cell-free therapy revealed by researchers – Drug Target Review | January 17th, 2020

Autologous stem cell and non-stem cell based therapies involve an individuals cell to be cultured and then re-introduced to the donors body. These therapies do not use foreign organism cells and are therefore free from HLA incompatibility, disease transmission, and immune reactions.Increasing demand for the new therapies in the field of regenerative medicine is directly facilitating the growth of autologous stem cell and non-stem cell based therapies market. Furthermore, since the risk to transplantation surgeries is significantly reduced in these therapies, they are increasingly being preferred for treatment of bone marrow diseases, aplastic anemia, multiple myeloma, non-Hodgkins lymphoma, Hodgkins lymphoma, Parkinsons disease, thalassemia, and diabetes.

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Moreover, rising incidents of cancer, diabetes and cardiovascular diseases along with growing geriatric population is another factor attributed for its high growth. However, side-effects of autologous stem cell and non-stem cell based therapies such as nausea, infection, hair loss, vomiting, diarrhea, etc. are expected to affect the market to an extent. High cost is another factor that can act as challenge to autologous stem cell and non-stem cell based therapies market. In spite of this, less risk post transplantation surgeries and favorable tax reimbursement policies are anticipated to reduce the impact of these limitation during the forecast period.Autologous stem cell and non-stem cell based therapies market can be segmented on the basis of application, end-user, and region.

In terms of application, the autologous stem cell and non-stem cell based therapies market can be segmented into blood pressure (BP) monitoring devices, intracranial pressure (ICP) monitoring devices, and pulmonary pressure monitoring devices. In terms of end-user, the market can be segmented into ambulatory surgical center and hospitals. By region, the market can be segmented into North America, Europe, Asia Pacific, Middle East and Africa and South America. Amongst all, Asia Pacific is anticipated to be the most attractive market owing to favorable reimbursement policies in the region.The players operating in autologous stem cell and non-stem cell based therapies market are limited.

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They are consistently involved in research and development activities for product development to keep up with the growing competition, thereby aiding the growth of autologous stem cell and non-stem cell based therapies market across the world.

The major players operating in autologous stem cell and non-stem cell based therapies market are Regennex, Antria(Cro), Bioheart, Orgenesis Inc., Virxys corporation , Dendreon Corporation, Tigenix, Georgia Health Sciences University, Neostem Inc, Genesis Biopharma, Brainstorm Cell Therapeutics, Tengion Inc., Fibrocell Science Inc., Opexa Therapeutics Inc, Regeneus Ltd, and Cytori Inc., among others.

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Autologous Stem Cell And Non Stem Cell Based Therapies Market Extracts Market, 2018-2026 by Segmentation Based on Product, Application and Region ...

Bone Marrow Stem Cells Comments Off on Autologous Stem Cell And Non Stem Cell Based Therapies Market Extracts Market, 2018-2026 by Segmentation Based on Product, Application and Region … | January 17th, 2020

Phoebe Roskell was just four-years-old when she became very unwell with bone marrow failure.

She became blood and platelet transfusion dependent and was told she needed a bone marrow transplant

Mum Jacquie Roskell, from Catterall, said after many hospital appointments and tests, doctors discovered that Phoebe had a rare and currently incurable disease called Dyskeratosis Congenita (DC).

The telomere biology disorder only affects one in a million people worldwide in which the telomeres - the caps at the end of each strand of DNA - are not present and therefore the DNA becomes damaged and cells cannot do their job.

This can lead to the premature ageing of cells and can cause life-threatening complications as well as shortened life expectency.

Jacquie Roskell, 43, from Catterall, told LancsLive: "In May 2017 Phoebe, then aged just 4-years-old, became very unwell and was found to be in bone marrow failure. She became blood and platelet transfusion dependent and we were told she would need a bone marrow transplant.

"In August of that year and after many tests it was discovered she had the rare and currently incurable disease Dyskeratosis Congenita (DC).

"DC is a telomere biology disorder and only affects one in a million people worldwide. Telomeres are the caps at the end of each strand of DNA that protect our chromosomes, like the plastic tips at the end of shoelaces. Without the coating, shoelaces become frayed until they can no longer do their job.

"Just as without telomeres, DNA strands become damaged and our cells cant do their job. This in turn causes premature ageing of cells such as bone marrow hence why Phoebes failed. Telomeres naturally shorten as we age, but Phoebe was born with exceptionally short telomeres like those of a 100-year-old woman."

Many life threatening complications can be cause by DC, such as liver and lung failure, higher chances of cancer and shortened life expectancy, says Jacquie.

Children with this mutation are unlikely to live longer than 16-year-old.

"There are currently 15 gene mutations identified with this disease and the one Phoebe has is called TINF2," Jacquie explained.

In December 2017, Phoebe's older brother Woody heroically donated his stem cells for her bone marrow transplant at The Royal Manchester Childrens Hospital. He saved her life.

The bone marrow failure was successful, however the disease had not yet been cured.

Jacquie, 43, said: "The treatment was gruelling, and her recovery was long and exhausting. The bone marrow failure was successfully cured but the disease is not.

"Phoebe suffers with episodes of extreme fatigue and exhaustion, joint pains, headaches and migraines. Injuries such as a sprained wrist take longer to heal for Phoebe, and she is still very susceptible to common viruses following her transplant.

"She attends many hospital appointments always in Manchester and is regularly seen by different medical teams including Haematology, Respiratory, ENT, Ophthalmology, Dental and Oral Medicine."

"Phoebe has suffered so much in her very short life. But when she is feeling well she is like a pocket rocket and there is just no stopping her. When she feels unwell she crashes and needs time to recover again,"

"The disease is unpredictable and although much research has been done into Telomere biology disorders there is still a long way to go.

"Much research is being carried out by the incredible charity Team Telomere - that support us as a family. Their aim is to hopefully find a cure for this cruel disease and fingers crossed it is in Phoebes lifetime."

That is why Jacquie is helping to fundraise for Team Telomere.

The charity supports families worldwide in their battle with DC and related Telomere Biology Disorders who often face multiple complex illnesses such as bone marrow failure, lung fibrosis, cancer, and many other challenges.

It also helps to encourage the medical communitys research in finding causes and effective treatments, and to facilitate improved diagnosis by educating medical providers.

To help raise money for Team Telamore, Jacquie is co-organising a pre-loved wedding sale along with her friend Samantha Smith who is the events manager of the Wyrebank in Garstang.

The sale will be held at Wyrebank on the Moorings on Sunday, March 1 from 11pm until 1pm.

Samantha told LancsLive: "The idea is for brides and businesses to sell their wedding items to future wedding couples.

"People can also donate wedding dresses and bridesmaid or we will take a percentage of the sales, and sell them for them."

Bridal stalls cost 15 and business stalls are 40.

All proceeds will be going to Team Telomere.

Alternatively, donations can be made directly via the website here.

You can also find more details on the Wyrebank pre-loved wedding sale here.

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The young girl diagnosed with 'one in a million' genetic disease - LancsLive

Bone Marrow Stem Cells Comments Off on The young girl diagnosed with ‘one in a million’ genetic disease – LancsLive | January 17th, 2020

Right now, your bodys stem cells are working hard replacing your skin every two weeks, creating new red and white blood cells and completing thousands of other tasks essential to life. They are your own personalized fountain of youth.

Scientists generally agree that a stem cell should be able to do both of the following:

One theory of ageing suggests that between the ages of 30 and 50, our stem cells reach a turning point and start to decline in number and function. This results in the typical features associated with ageing.

There does not seem to be a single discoverer of stem cells. Accounts date back to the 1800s and even further, but the first successful medical procedure was a bone marrow transfusion in 1939. Advances in immunology led to donor matching, initially via siblings and close relatives. Unrelated donor matching flourished in the 1970s, alongside donor registries.

In the 1980s, scientists identified embryonic stem cells in mice, leading to the 1997 cloning of Dolly the Sheep. This created immense interest for human and medical applications and a backlash in the US as federal R&D funding was essentially halted in 2001.

In 2012, a Nobel Prize was awarded for the earlier discovery of induced pluripotent stem cells (iPS). Essentially, they return potency and self-renewal properties to mature non-stem cells, essentially making them act like stem cells again.

In the decade between 2010 and 2019, the first wave of stem cell start-ups emerged, alongside R&D programmes at many large pharmaceutical companies, leading to innovation and the first human clinical trials for iPS and other related therapies.

According to Q3 2019 data from the Alliance for Regenerative Medicine, there are 959 regenerative medicine companies worldwide sponsoring 1,052 active clinical trials; 525 of these companies are in North America, 233 in Europe and Israel, and 166 in Asia. In aggregate, $7.4 billion has been invested in regenerative medicine companies in 2019; $5.6 billion of which has been dedicated to gene and gene-modified cell therapy, $3.3 billion in cell therapy, and $114 million in tissue engineering.

Overview of the cancer stem cells market

Perhaps most excitingly, curative therapies are hitting the market and the results are astonishing: 60% of Acute Lymphoblastic Leukemia patients taking Novartis Kymirah showed a complete response (no traces of cancer) and were declared in full remission. Meanwhile, 75% of patients with Transfusion-Dependent -Thalassaemia treated with bluebird bios Zynteglo achieved independence from transfusions. Perhaps most astonishingly, 93% of spinal muscular atrophy patients treated with Novartis Zolgensma were alive without permanent ventilation 24 months after treatment. We should expect more medical breakthroughs in the coming years.

New science, new start-ups: several companies in the sector have gone public or been acquired. These exits led to the recycling of talent and capital into new companies. Because the science and commercial systems have also advanced, the companies in the next wave are pursuing bigger challenges, driving innovation, with even greater resources.

Patients are eager: the current market for stem cell therapies is growing at 36% per year, though it will rapidly expand when a breakthrough occurs toward the treatment of a non-communicable disease (such as cancer, diabetes, heart disease) or a lifestyle factor (for example, growing hair in the correct places, expanding cognitive abilities or increasing healthy lifespan).

New R&D models: funding is flowing into the sector from large companies, VC funds, and institutions such as the California Institute for Regenerative Medicine (CIRM) and New York State Stem Cell Science programme (NYSTEM). Some of the leading university R&D platforms include the Center for the Commercialization of Regenerative Medicine in Toronto, the Stanford Institute for Stem Cell Biology and Regenerative Medicine, the Oxford Stem Cell Institute, and most notably, the Harvard Stem Cell Institute (HSCI).

Founded in 2004, HSCI has established a phenomenal track record. It provided the first $200,000 in funding to Derrick Rossis lab, which inspired the largest biotech IPO to date. HSCI scientists were also co-founders or principals in the three most prominent gene-editing companies (CRISPR Tx, Intellia and Editas), the combined $1.55-billion True North/iPierian acquisitions and the recent $950-million acquisition of Semma Tx, Frequency Tx, Fate Tx, Epizyme Inc., and Magenta Tx.

For the casual investor, Evercore ISI is building a Regenerative Medicine Index, which may be the simplest way to build a portfolio. For institutions and those with deeper pockets, regenerative medicine funds are forming, including the Boston-centric Hexagon Regenerative Medicine Fund, which aims to create companies out of the Harvard Stem Cell Institute.

Caveat emptor. Though patients needs are immediate, those seeking treatments should think very carefully about the risks. There are many dubious clinics touting expensive stem cell treatments and some patients have experienced horrifying complications. Dr. Paul Knoepfler of UC-Davis has written a practical and scientifically accurate guide, a strongly recommended read if you or a family member are considering treatment or a clinical trial.

The leading causes of death in 1900 were mostly infectious/communicable diseases. While the prevalence of most causes has diminished, the largest increases include heart disease (+40%) and cancer (+300%). Granted, this is partly due to doubling life expectancy and a lack of death from other causes. However, given time and resources, scientists and physicians may cure these challenging diseases.

Total disease burden by disease or injury

Today, six of the seven leading causes of death are non-communicable diseases (heart disease, stroke, lung diseases, cancer, Alzheimers disease and diabetes). Based on the early promise mentioned above, regenerative medicine may be our best hope to solve the great non-communicable diseases of our time, and perhaps the single most transformative medical innovation in a century.

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The views expressed in this article are those of the author alone and not the World Economic Forum.

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Why stem cells could be the medical innovation of the century - World Economic Forum

Skin Stem Cells Comments Off on Why stem cells could be the medical innovation of the century – World Economic Forum | January 17th, 2020

WASHINGTON - Scientists in the United States created the first living robots using stem cells, which can move toward a target and heal themselves after being cut. A study published on Monday in Proceedings of the National Academy of Sciences described the living, programmable organism, a completely new biological machine designed from ground up. Scientists at the University of Vermont ran an evolutionary algorithm on a supercomputer to screen out a design to be composed of single frog skin and heart cells.

Then, scientists at Tufts University transferred the in silico design into life with stem cells harvested from embryos of African frogs. They used tiny forceps and electrode to assemble the single cells into a close approximation of the computer designs.

They found that the skin cells formed a more passive architecture, while the once-random contractions of heart muscle cells were put to work creating ordered forward motion, allowing the robots to move on their own.

Those millimeter-wide reconfigurable organisms were shown to be able to move and explore their watery environment for days or weeks, according to the study.

They could move around in circles, collectively pushing pellets into a central location. Its a step toward using computer-designed organisms for intelligent drug delivery, said Joshua Bongard, a computer scientists at the University of Vermont.

We can imagine many useful applications of these living robots that other machines cant do, said Michael Levin at Tufts University, like searching out nasty compounds or radioactive contamination, gathering microplastic in the oceans, traveling in arteries to scrape out plaque.

In another test, the scientists cut the living robots and watched what happened. We sliced the robot almost in half and it stitches itself back up and keeps going, said Bongard.

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US scientists build first robot made of living cells - The Nation

Skin Stem Cells Comments Off on US scientists build first robot made of living cells – The Nation | January 17th, 2020

Remember Black Mirrors Metalhead episode where a robot dog shoots the protagonist with trackers in the face? The thought of having unwanted foreign intruders attacking us from inside was absolutely nightmarish. We might have something similar now, as scientists strive to innovate to create new and novel micro-robots every day, but, with scientific and sane intentions.

Now, researchers at the University of Vermont and Tufts University have created living robots out of actual healthy frog cells that have the potential to navigate through one's bloodstream and scrape out plaque from arteries. These robots, called xenobots, are essentially a bioengineering product made by harvesting skin, pumping heart cells from frogs, and clumping them with stem cells from its embryo. Whats more? They are fully biodegradable and self-healing!

According to a press release, scientists first used a supercomputer to design the new life-form that can move in a direction. After having created a biological model of the supercomputers vision, they assembled the clusters with the beating cardiac cells on one end acting as a pump to propel the clump forward through the water.

Using this technique, the team created a number of the living robots and watched as they were able to successfully push other objects around. The researchers also experimented with creating a pouch inside the new life-forms, allowing them to carry a payload around. Despite of having a very low motility, these robots can perform task that other machines cant do, like searching out nasty compounds or radioactive contamination, gathering microplastic in the oceans and so on. And while they may not be as strong as metals, theyre regenerative.

The notion of having living organisms inside our body, that can possibly be programmed for malicious intent, is nerve-wracking. With xenobots, scientists wish to resolve this fear and work on tackling the unintended consequences. A paper detailing the research was published in the Proceedings of the National Academy of Sciences.

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Scientists Turn Frog Cells Into Tiny Living Robots That Can Swim Through Your Body! - Mashable India

Cardiac Stem Cells Comments Off on Scientists Turn Frog Cells Into Tiny Living Robots That Can Swim Through Your Body! – Mashable India | January 17th, 2020

Scientists from the University of Vermont (UVM) and Tufts University in Massachusetts said on January 13, 2020, that theyve now assembled living cells into entirely new life-forms. They call them living robots, or xenobots for the frog species from whose cells the little robots sprang. The scientists describe them as tiny blobs, submillimeter in size (a millimeter is about 1/25th of an inch, so these little blobs are smaller than that). The blobs contain between 500 and 1,000 cells. They can heal themselves after being cut. The blobs have been able to scoot across a petri dish, self-organize, and even transport minute payloads. Maybe, eventually, theyll be able to carry a medicine to a specific place inside a human body, scrape plaque from arteries, search out radioactive contamination, or gather plastic pollution in Earths oceans.

And, yes, the scientists do acknowledge possible ethical issues. More about that below.

Joshua Bongard, a computer scientist and robotics expert at the University of Vermont who co-led the new research, said in a statement:

These are novel living machines. Theyre neither a traditional robot nor a known species of animal. Its a new class of artifact: a living, programmable organism

You look at the cells weve been building our xenobots with, and, genomically, theyre frogs. Its 100% frog DNA but these are not frogs. Then you ask, well, what else are these cells capable of building?

The results of the new research were published January 13 in the Proceedings of the National Academy of Sciences.

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A manufactured quadruped (4-footed) organism, 650-750 microns in diameter (a micron is a millionth of a meter). The scientists described this creature (if we can call it a creature) as a bit smaller than a pinhead. Image via Douglas Blackiston/ Tufts University/ University of Vermont.

In their published paper, these scientists wrote:

Most technologies are made from steel, concrete, chemicals, and plastics, which degrade over time and can produce harmful ecological and health side effects. It would thus be useful to build technologies using self-renewing and biocompatible materials, of which the ideal candidates are living systems themselves. Thus, we here present a method that designs completely biological machines from the ground up: computers automatically design new machines in simulation, and the best designs are then built by combining together different biological tissues. This suggests others may use this approach to design a variety of living machines to safely deliver drugs inside the human body, help with environmental remediation, or further broaden our understanding of the diverse forms and functions life may adopt.

The new creatures were designed on a supercomputer at UVM, and then assembled and tested by biologists at Tufts University. The scientists statement described their process this way:

With months of processing time on the Deep Green supercomputer cluster at UVMs Vermont Advanced Computing Core, the team including lead author and doctoral student Sam Kriegman of UVM [@Kriegmerica on Twitter] used an evolutionary algorithm to create thousands of candidate designs for the new life-forms. Attempting to achieve a task assigned by the scientists like locomotion in one direction the computer would, over and over, reassemble a few hundred simulated cells into myriad forms and body shapes. As the programs ran driven by basic rules about the biophysics of what single frog skin and cardiac cells can do the more successful simulated organisms were kept and refined, while failed designs were tossed out. After a hundred independent runs of the algorithm, the most promising designs were selected for testing.

Then the team at Tufts, led by Michael Levin and with key work by microsurgeon Douglas Blackiston transferred the in-silico designs into life. First they gathered stem cells, harvested from embryos of African frogs, the species Xenopus laevis [African clawed frogs; hence the name xenobots.]

These were separated into single cells and left to incubate. Then, using tiny forceps and an even tinier electrode, the cells were cut and joined under a microscope into a close approximation of the designs specified by the computer.

Assembled into body forms never seen in nature, the cells began to work together. The skin cells formed a more passive architecture, while the once-random contractions of heart muscle cells were put to work creating ordered forward motion as guided by the computers design, and aided by spontaneous self-organizing patterns allowing the robots to move on their own.

These reconfigurable organisms were shown to be able move in a coherent fashion and explore their watery environment for days or weeks, powered by embryonic energy stores. Turned over, however, they failed, like beetles flipped on their backs.

Later tests showed that groups of xenobots would move around in circles, pushing pellets into a central location spontaneously and collectively. Others were built with a hole through the center to reduce drag. In simulated versions of these, the scientists were able to repurpose this hole as a pouch to successfully carry an object.

Wow yes?

The scientists said they see this work as part of a bigger picture. And they acknowledged that some may fear the implications of rapid technological change and complex biological manipulations. Levin commented:

That fear is not unreasonable. When we start to mess around with complex systems that we dont understand, were going to get unintended consequences.

However, he said:

If humanity is going to survive into the future, we need to better understand how complex properties, somehow, emerge from simple rules.

He said much of science is focused on:

controlling the low-level rules. We also need to understand the high-level rules.

I think its an absolute necessity for society going forward to get a better handle on systems where the outcome is very complex. A first step towards doing that is to explore: how do living systems decide what an overall behavior should be and how do we manipulate the pieces to get the behaviors we want?

In other words, he said:

this study is a direct contribution to getting a handle on what people are afraid of, which is unintended consequences.

Bongard added:

Theres all of this innate creativity in life. We want to understand that more deeply and how we can direct and push it toward new forms.

On the left, the anatomical blueprint for a computer-designed organism, discovered on a UVM supercomputer. On the right, the living organism, built entirely from frog skin (green) and heart muscle (red) cells. The background displays traces carved by a swarm of these new-to-nature organisms as they move through a field of particulate matter. Image via Sam Kriegman/ UVM.

Bottom line: Scientists said in early January 2020 that theyve created the first living robots, or xenobots, assembled from the cells of frogs. Their creators promise advances from drug delivery to toxic waste clean-up.

Source: A scalable pipeline for designing reconfigurable organisms

Via UVM

Read more:
Team builds the 1st living robots - EarthSky

Cardiac Stem Cells Comments Off on Team builds the 1st living robots – EarthSky | January 17th, 2020

UpMarketResearch.com, has added the latest research on Dry Powder Inhaler Market, which offers a concise outline of the market valuation, industry size, SWOT analysis, revenue approximation, and the regional outlook of this business vertical. The report precisely features the key opportunities and challenges faced by contenders of this industry and presents the existing competitive setting and corporate strategies enforced by the Dry Powder Inhaler Market players.

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Original post:
Autologous Stem Cell Based Therapies Market Report Analysis, Share, Revenue, Growth Rate With Forecast Overview To 2024 - Fusion Science Academy

Cardiac Stem Cells Comments Off on Autologous Stem Cell Based Therapies Market Report Analysis, Share, Revenue, Growth Rate With Forecast Overview To 2024 – Fusion Science Academy | January 17th, 2020

14 January 2020

These millimetre-wide "xenobots" can move toward a target, perhaps pick up a payload (like a medicine that needs to be carried to a specific place inside a patient) and heal themselves after being cut.

"These are novel living machines," says Joshua Bongard, a computer scientist and robotics expert at the University of Vermont who co-led the new research. "They're neither a traditional robot nor a known species of animal. It's a new class of artefact: a living, programmable organism."

The new creatures were designed on a supercomputer at UVM and then assembled and tested by biologists at Tufts University. "We can imagine many useful applications of these living robots that other machines can't do," says co-leader Michael Levin who directs the Centre for Regenerative and Developmental Biology at Tufts, "like searching out nasty compounds or radioactive contamination, gathering microplastic in the oceans, traveling in arteries to scrape out plaque."

The results of the new research were published January 13 in the Proceedings of the National Academy of Sciences.

Bespoke living systems

People have been manipulating organisms for human benefit since at least the dawn of agriculture, genetic editing is becoming widespread, and a few artificial organisms have been manually assembled in the past few years copying the body forms of known animals.

But this research, for the first time ever, "designs completely biological machines from the ground up," the team writes in their new study.

With months of processing time on the Deep Green supercomputer cluster at UVM's Vermont Advanced Computing Core, the team including lead author and doctoral student Sam Kriegman used an evolutionary algorithm to create thousands of candidate designs for the new life-forms. Attempting to achieve a task assigned by the scientists like locomotion in one direction the computer would, over and over, reassemble a few hundred simulated cells into myriad forms and body shapes. As the programs ran driven by basic rules about the biophysics of what single frog skin and cardiac cells can do the more successful simulated organisms were kept and refined, while failed designs were tossed out. After a hundred independent runs of the algorithm, the most promising designs were selected for testing.

Then the team at Tufts, led by Levin and with key work by microsurgeon Douglas Blackiston, transferred the in-silico designs into life. First, they gathered stem cells, harvested from the embryos of African frogs, the species Xenopus laevis. (Hence the name "xenobots.") These were separated into single cells and left to incubate. Then, using tiny forceps and an even tinier electrode, the cells were cut and joined under a microscope into a close approximation of the designs specified by the computer.

Assembled into body forms never seen in nature, the cells began to work together. The skin cells formed a more passive architecture, while the once-random contractions of heart muscle cells were put to work creating ordered forward motion as guided by the computer's design and aided by spontaneous self-organising patterns allowing the robots to move on their own.

These reconfigurable organisms were shown to be able move in a coherent fashion and explore their watery environment for days or weeks, powered by embryonic energy stores. Turned over, however, they failed, like beetles flipped on their backs.

Later tests showed that groups of xenobots would move around in circles, pushing pellets into a central location spontaneously and collectively. Others were built with a hole through the centre to reduce drag. In simulated versions of these, the scientists were able to repurpose this hole as a pouch to successfully carry an object. "It's a step toward using computer-designed organisms for intelligent drug delivery," says Bongard, a professor in UVM's Department of Computer Science and Complex Systems Centre.

Living technologies

Many technologies are made of steel, concrete or plastic. That can make them strong or flexible. But they also can create ecological and human health problems, like the growing scourge of plastic pollution in the oceans and the toxicity of many synthetic materials and electronics. "The downside of living tissue is that it's weak and it degrades," says Bongard. "That's why we use steel. But organisms have 4.5 billion years of practice at regenerating themselves and going on for decades." And when they stop working death they usually fall apart harmlessly. "These xenobots are fully biodegradable," say Bongard, "when they're done with their job after seven days, they're just dead skin cells."

Your laptop is a powerful technology. But try cutting it in half. Doesn't work so well. In the new experiments, the scientists cut the xenobots and watched what happened. "We sliced the robot almost in half and it stitches itself back up and keeps going," says Bongard. "And this is something you can't do with typical machines."

Cracking the Code

Both Levin and Bongard say the potential of what they've been learning about how cells communicate and connect extends deep into both computational science and our understanding of life. "The big question in biology is to understand the algorithms that determine form and function," says Levin. "The genome encodes proteins, but transformative applications await our discovery of how that hardware enables cells to cooperate toward making functional anatomies under very different conditions."

To make an organism develop and function, there is a lot of information sharing and cooperation organic computation going on in and between cells all the time, not just within neurons. These emergent and geometric properties are shaped by bioelectric, biochemical, and biomechanical processes, "that run on DNA-specified hardware," Levin says, "and these processes are reconfigurable, enabling novel living forms."

The scientists see the work presented in their new PNAS study "A scalable pipeline for designing reconfigurable organisms," as one step in applying insights about this bioelectric code to both biology and computer science. "What actually determines the anatomy towards which cells cooperate?" Levin asks. "You look at the cells we've been building our xenobots with, and, genomically, they're frogs. It's 100% frog DNA but these are not frogs. Then you ask, well, what else are these cells capable of building?"

"As we've shown, these frog cells can be coaxed to make interesting living forms that are completely different from what their default anatomy would be," says Levin. He and the other scientists in the UVM and Tufts team with support from DARPA's Lifelong Learning Machines program and the National Science Foundation believe that building the xenobots is a small step toward cracking what he calls the "morphogenetic code," providing a deeper view of the overall way organisms are organised and how they compute and store information based on their histories and environment.

Many people worry about the implications of rapid technological change and complex biological manipulations. "That fear is not unreasonable," Levin says. "When we start to mess around with complex systems that we don't understand, we're going to get unintended consequences." A lot of complex systems, like an ant colony, begin with a simple unit an ant from which it would be impossible to predict the shape of their colony or how they can build bridges over water with their interlinked bodies.

"If humanity is going to survive into the future, we need to better understand how complex properties, somehow, emerge from simple rules," says Levin. Much of science is focused on "controlling the low-level rules. We also need to understand the high-level rules," he says. "If you wanted an anthill with two chimneys instead of one, how do you modify the ants? We'd have no idea."

"I think it's an absolute necessity for society going forward to get a better handle on systems where the outcome is very complex," Levin says. "A first step towards doing that is to explore: how do living systems decide what an overall behaviour should be and how do we manipulate the pieces to get the behaviours we want?"

In other words, "this study is a direct contribution to getting a handle on what people are afraid of, which is unintended consequences," Levin says whether in the rapid arrival of self-driving cars, changing gene drives to wipe out whole lineages of viruses, or the many other complex and autonomous systems that will increasingly shape the human experience.

"There's all of this innate creativity in life," says UVM's Josh Bongard. "We want to understand that more deeply and how we can direct and push it toward new forms."

Information courtesy of University of Vermont

Excerpt from:
- Team builds first living robots using frog cells - Design Products & Applications

Cardiac Stem Cells Comments Off on – Team builds first living robots using frog cells – Design Products & Applications | January 17th, 2020

Under normal circumstances the stem cells of frog embryos would skin and heart tissue of living beings, however, the progress of scientific knowledge has turned them into the first ever living robots.

Scientists from the University of Vermont with the help of special algorithms modified stem cells of a frog and created of them the first xenobot clumps of cells, capable of self-organization and even to transport tiny cargo. These colonies of 500-1000 cells do not resemble any living organism, or a naturally functioning body. At the same time they are different from the traditional robot is alive, but programmed organisms.

The opportunity to design a live guided machine, able to perform various tasks, from drug delivery to environmental cleanup, is truly revolutionary.

To create xenobot required a supercomputer and an algorithm that assemble in the desired configuration, hundreds of heart cells and skin tissue and simulates the result of such a living designer. The least successful configuration of the scientists involved in the experiment, culled, best preserved and improved using manipulations of the cells of the African frog Xenopus laevis microscopic tweezers and the electrode.

In one of the configurations, the scientists there is a hole in the center of the clot to reduce the resistance when driving. The experiment revealed that it can be used to attach to the get of goods for transportation.

After completing the Assembly of the fabric of biorobots began to operate at the programmed scenario: the skin cells began to group together, and provided the cardiac motor function. In an aqueous medium in the Petri dish these living machines can move up to a week without nutrient requirements energy supply inherent nature in the form of lipids and proteins.

Scientists say that this experiment gives an invaluable experience of knowing how cells communicate and exchange information:

From the point of view of the genome, its a frog. 100% DNA xenobot corresponds to the frog, but not frog. The question arises what else can be built from these cells? says biologist Michael Levin. This experiment shows us that frog cells can form life-forms that have nothing to do with the fact that they were anatomically.

However, living these robots can be called only conditionally they are not able to develop, you do not have the reproductive function and cant reproduce without the will of man, and, having exhausted all the resources of nutrients, they turn into lumps of dead cells (100% Biodegradability is a clear advantage of biological robots before the metal or plastic robots).

So far, the level of development xenobot seems completely harmless, but in the future they can enrich and nerve cells or even to turn into a new form of biological weapons.

Under normal circumstances the stem cells of frog embryos would skin and heart tissue of living beings, however, the progress of scientific knowledge has turned them into the first ever living robots.

Scientists from the University of Vermont with the help of special algorithms modified stem cells of a frog and created of them the first xenobot clumps of cells, capable of self-organization and even to transport tiny cargo. These colonies of 500-1000 cells do not resemble any living organism, or a naturally functioning body. At the same time they are different from the traditional robot is alive, but programmed organisms.

The opportunity to design a live guided machine, able to perform various tasks, from drug delivery to environmental cleanup, is truly revolutionary.

To create xenobot required a supercomputer and an algorithm that assemble in the desired configuration, hundreds of heart cells and skin tissue and simulates the result of such a living designer. The least successful configuration of the scientists involved in the experiment, culled, best preserved and improved using manipulations of the cells of the African frog Xenopus laevis microscopic tweezers and the electrode.

In one of the configurations, the scientists there is a hole in the center of the clot to reduce the resistance when driving. The experiment revealed that it can be used to attach to the get of goods for transportation.

After completing the Assembly of the fabric of biorobots began to operate at the programmed scenario: the skin cells began to group together, and provided the cardiac motor function. In an aqueous medium in the Petri dish these living machines can move up to a week without nutrient requirements energy supply inherent nature in the form of lipids and proteins.

Scientists say that this experiment gives an invaluable experience of knowing how cells communicate and exchange information:

From the point of view of the genome, its a frog. 100% DNA xenobot corresponds to the frog, but not frog. The question arises what else can be built from these cells? says biologist Michael Levin. This experiment shows us that frog cells can form life-forms that have nothing to do with the fact that they were anatomically.

However, living these robots can be called only conditionally they are not able to develop, you do not have the reproductive function and cant reproduce without the will of man, and, having exhausted all the resources of nutrients, they turn into lumps of dead cells (100% Biodegradability is a clear advantage of biological robots before the metal or plastic robots).

So far, the level of development xenobot seems completely harmless, but in the future they can enrich and nerve cells or even to turn into a new form of biological weapons.

See original here:
The first robots (xenobot) from living cells use cells of a frog - http://www.MICEtimes.asia

Cardiac Stem Cells Comments Off on The first robots (xenobot) from living cells use cells of a frog – www.MICEtimes.asia | January 17th, 2020

Forget gleaming metal droids -- the robots of the future may have more in common with the average amphibian than with R2D2.

A team of scientists have found a way to not just program a living organism, but to build brand new life-forms from scratch using cells, creating what researchers are calling xenobots.

Tiny in size, but vast in potential, these millimetre-sized bots could potentially be programmed to help in medical procedures, ocean cleanup and investigating dangerous compounds, among other things.

"They're neither a traditional robot nor a known species of animal, said researcher Joshua Bongard in a news release. It's a new class of artifact: a living, programmable organism."

In the introduction for the research published in Proceedings of the National Academy of Sciences (PNAS) on Monday, researchers point out that the traditional building blocks weve used for robots and tech -- steel, plastic, chemicals, etc. -- all degrade over time and can produce harmful ecological and health side-effects.

After realizing that the best self-renewing and biocompatible materials would be living systems themselves, researchers decided to create a method that designs completely biological machines from the ground up.

The bots are made out of stem cells taken from frog embryos -- specifically, an African clawed frog called xenopus laevis, which supplied the inspiration for the name xenobot. To design the xenobots, the possible configurations of different cells were first modeled on a supercomputer at the University of Vermont.

The designs then went to Tufts University, where the embryonic cells were collected and separated to develop into more specialized cells. Then, like sculptors (if sculptors used microsurgery forceps and electrodes), biologists manually shaped the cells into clumps that matched the computer designs.

Different structures were sketched out by the computer in accordance with the scientists goal for each xenobot.

For example, one xenobot was designed to be able to move purposely in a specific direction. To achieve this, researchers put cardiac cells on the bottom of the xenobot. These cells naturally contract and expand on their own, meaning that they could serve as the xenobots engine, or legs, and help move the rest of the organism, which was built out of more static skin cells.

In order to test if the living robots were truly moving the way they were designed to, and not just randomly, researchers performed a test that has stumped many a living creature.

They flipped the robot on its back. And just like a capsized turtle, it could no longer move.

When researchers created further designs for the bots, they found that they could design them to push microscopic objects, and even carry objects through a pouch.

"It's a step toward using computer-designed organisms for intelligent drug delivery," says Bongard.

The possible uses for these tiny robots are numerous, researchers say.

In biomedical settings, one could envision such biobots (made from the patients own cells) removing plaque from artery walls, identifying cancer, or settling down to differentiate or control events in locations of disease, the research paper suggests.

A robot made out of metal or steel generally has to be repaired by human hands if it sustains damage. One major benefit that researchers found of creating these robots out of living cells was how they reacted to physical damage.

A video taken by the researchers showed that when one of their organisms was cut almost in half by metal tweezers, the two sides of the wound simply stitched itself back together.

These living robots, researchers realized, could repair themselves automatically, something you cant do with typical machines, Bongard said.

Because they are living cells, they are also naturally biodegradable, Bongard pointed out. Once theyve fulfilled their purpose, theyre just dead skin cells, making them even more optimal for usage in medical or environmental research.

Although scientists have been increasingly manipulating genetics and biology, this is the first time that a programmable organism has been created from scratch, researchers say.

This new research takes scientists a step closer to answering just how different cells work together to execute all of the complex processes that occur every day in animals and humans.

"The big question in biology is to understand the algorithms that determine form and function," said co-leader Michael Levin in the press release. He directs the Center for Regenerative and Developmental Biology at Tufts.

"What actually determines the anatomy towards which cells co-operate? he asked. You look at the cells we've been building our xenobots with, and, genomically, they're frogs. It's 100 per cent frog DNA -- but these are not frogs. Then you ask, well, what else are these cells capable of building? As we've shown, these frog cells can be coaxed to make interesting living forms that are completely different from what their default anatomy would be.

Of course, a biological organism created and programmed by humans which is capable of healing itself might sound a little alarming. After all, one of the sponsors of the research is the Defense Advanced Research Projects Agency, which is affiliated with the U.S. military.

Researchers acknowledged in the press release that the implications around such technological and biological advancements can be worrying at times.

That fear is not unreasonable, Levin said. However, he believes that in order to move forward with science, we should not hold back from complex questions. This study is a direct contribution to getting a handle on what people are afraid of, which is unintended consequences.

"I think it's an absolute necessity for society going forward to get a better handle on systems where the outcome is very complex," Levin says. "A first step towards doing that is to explore: how do living systems decide what an overall behavior should be and how do we manipulate the pieces to get the behaviors we want?"

More on this story from CTVNews.ca

See original here:
The 'xenobot' is the worlds newest robot and it's made from living animal cells - The Loop

Cardiac Stem Cells Comments Off on The ‘xenobot’ is the worlds newest robot and it’s made from living animal cells – The Loop | January 17th, 2020

Plus, these new robots can heal themselves after being cut, giving them a longer life span. "They're neither a traditional robot nor a known species of animal. It's a new class of artifact: a living, programmable organism," notes Joshua Bongard, a computer scientist and robotics expert at the University of Vermont who co-led the new research.

The live robots were designed and developed on a supercomputer at UVM and then tested by biologists at Tufts University. The idea of manipulating living organisms and copying body forms for human benefit isn't something new. However, this is the first time scientists have developed biological machines from scratch.

The team led by lead author and doctoral student Sam Kriegman, used an evolutionary algorithm to develop thousands of candidate designs for the new life-forms on the Deep Green supercomputer and was published in PANS. The program was fed the basic rules about biophysics of what a single frog skin and cardiac cells were capable of.

Nearly a hundred independent algorithm runs were conducted to select the most promising designs. Next, the team at Tufts worked with microsurgeon to transfer the silicon designs into life. Stem cells from an African frog (Xenopus lavevis, giving the name Xenobots) were harvested in the embryos. Assembled into body forms, the cells began working together.

Many of our gadgets and other technologies are made of steel, plastic, silicon. While it makes it strong and flexible, it also creates an ecological imbalance and human health problems. Bongard notes that living tissues are weak and degrade quickly. "But organisms have 4.5 billion years of practice at regenerating themselves and going on for decades," he says.

Even when tissues die, they're harmless to the environment. What's more interesting is that the live robots were sliced into half and surprisingly, it stitched itself and kept going. "This is something you can't do with typical machines," Bongard says. This is organic computation, which the authors explain as the information is shared and cooperated between cells.

The reconfigured organisms were found moving coherently and could explore watery environments for days and weeks together. The immediate application the researchers are suggesting is healthcare, where the Xenobots can be sent to pick a payload like medicine and carry it to the specific place inside the patient.

What About Ill-Effects?

Of course, the concerns on rapid changes in technology and complex biological manipulations have been rising. "When we start to mess around with complex systems that we don't understand, we're going to get unintended consequences," the scientists agree. At the same time, researchers note that a better understanding of complex properties is essential for mankind to survive.

See original here:
Scientists Develop Live Robots With Frog Cells That Might Redefine Healthcare - Gizbot

Cardiac Stem Cells Comments Off on Scientists Develop Live Robots With Frog Cells That Might Redefine Healthcare – Gizbot | January 17th, 2020

SAN DIEGO--(BUSINESS WIRE)-- Allele Biotechnology and Pharmaceuticals, Inc. (President and CEO: Jiwu Wang, Ph.D., Allele), a San Diego-based private company, and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., Astellas), through its Massachusetts-based subsidiary Astellas Institute for Regenerative Medicine (AIRM), entered into a licensing agreement to expand Astellas access to Alleles induced pluripotent stem cell (iPSC) technologies for various cell therapy programs.

Astellas, one of the largest pharmaceutical companies in Japan and already a leader in the development of cell-based therapeutics, has further dedicated to development of the field through its commitment to state-of-the-art iPS cell generation, modification, and manufacturing. iPSC lines can differentiate into all somatic tissue types, enabling a wide variety of therapeutic applications. The field of iPSC-derived cells has seen dramatic growth in clinical trials recently--the majority of the ~12 clinical trials around the world were initiated within the last 18 months and many more are upcoming.

Allele has been developing its core strength in reprogramming somatic cells into iPSCs with granted patents and the first commercial cGMP system it developed over the past 10 years. Allele also engages in more than a dozen different human tissue derivation activities through its own R&D efforts for internal programs and partnerships. To realize the unparalleled potential of iPSC, Alleles researchers and cGMP team are committed to setting up and validating cell assays for product quality control, genome analysis pipelines, closed-system automation for reprogramming, and machine learning in iPSC-related fields.

Under the terms of the new license agreement, Astellas will pay Allele upfront and milestones, product-based royalties, and potentially manufacture fees.

About Allele Allele Biotechnology and Pharmaceuticals was founded in 1999. In 2015, the company completed an 18,000 square foot state-of-the-art facility in San Diego for the production of GMP-grade human iPSC lines. The facility also supports the production of tissue-specific cells differentiated from these iPSCs, including pancreatic beta cells, neural progenitor cells, and cardiomyocytes.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200113005668/en/

View original post here:
Allele and Astellas Enter into an Expanded License for the Development of iPSC Lines - BioSpace

IPS Cell Therapy Comments Off on Allele and Astellas Enter into an Expanded License for the Development of iPSC Lines – BioSpace | January 16th, 2020

Otology sponges are cotton balls used after otology surgery. They are placed in the ear to hold the skin and eardrum in place after otology surgery. After otology surgery, the ear canal is packed with antibiotic ointment and otology sponges. Myringotomy with the insertion of tympanostomy tubes is the most common ontology surgical procedure in the U.S., and approximately 2 million procedures conducted each year. The field of otology has witnessed remarkable advancements in the management of complex ailments, such as hearing disorders, through the ongoing progress of sophisticated intricate and microscopic surgeries.

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Most common causes of surgeries are the retraction of the tympanic membrane, chronic otitis media and collapsed eustachian tube. Otology sponges are sterile devices used post-surgery for 6 weeks or for a month. Otology surgeries are mostly performed in outpatient systems and they do not require overnight stay. Since patients can go outdoor immediately after surgery, the chances of wound infection increase.

To prevent infection, these sponges are placed in ear canal with the lubrication of antibiotics. Sometimes, an incision is made behind the year to operate the internal canal. In this situation, sterile dressings along with antibiotic lubricants are placed over the stiches to prevent microbial infection. Owing to the shape of the ear, there is very less pace to operate inside it, owing to which otology surgeries are performed with the help of microscopes for greater accuracy and success. Increase in the number of ENT specialists, coupled with the availability of technologically sound surgical methods, is boosting the number of otology surgeries.

Otology Sponges Market: Drivers and Restraints

An increase in the number of otology surgeries due to the availability of advanced surgical methods is expected to drive the market. Advanced methods of otology surgeries have spread significantly in the developing world, which is also contributing to the growth of the market. Ease of use due to flexibility and the compressed configuration of these sponges is also driving the market.

Otology sponges are sterile and available in different sizes, hence, they are effective in preventing ear canal infections. Increase in awareness about the availability of otology surgical treatment is contributing to market growth. The effectiveness of otology sponges in preventing ear canal infections and holding the shape of the eardrum is driving the market. However, low awareness among the general public about their usage is restraining market growth.

Otology Sponges Market: Segmentation

The global otology sponges market can be segmented on the basis of material, end user type and geography.

Based on material type, the otology sponges market is segmented as:

Based on end use, the otology sponges market is segmented as:

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Otology Sponges Market: Overview

The global otology sponges market is expected to grow steadily owing to an increase in the number of otology surgeries. Advanced technological intervention for otology surgeries is also boosting the otology sponges market. By material type, the otology sponges market is expected to be dominated by latex-free otology sponges. By end users, the otology sponges market is expected to be dominated by ENT clinics owing to an increase in the number of outpatient surgeries. The widespread availability of otology sponges in different sizes makes them easy to use and one can wear them comfortably. Moreover, the number of otology surgical procedures has increased in developing countries as well, which is boosting the market in these countries.

Otology Sponges Market: Regional Outlook

The global otology sponges market is majorly dominated by North America owing to a significant number of otology surgical procedures in the region. Europe is the second most lucrative market owing to the availability of advanced otology surgical methods. Asia Pacific is expected to emerge as one of the most lucrative otology sponges markets owing to an increase in awareness about otology surgical treatments. Emerging economies, such as China and India, are potential markets for otology sponges because of their large population base. Latin America is also a lucrative market owing to the higher adoption of otology sponges. However, the Middle East and Africa is the least lucrative otology sponges market due to lack of awareness and the low availability of advanced otology surgical methods.

Otology Sponges Market: Key Players

Some of the global key players operating in otology sponges market areDeRoyal Industries, Inc.; Boston Medical Products, Inc.; Summit Medical, Inc.; American Surgical Company LLC; Medtronic and Olympus Corporation.

The report is a compilation of first-hand information, qualitative and quantitative assessment by industry analysts, inputs from industry experts and industry participants across the value chain. The report provides in-depth analysis of parent market trends, macro-economic indicators and governing factors along with market attractiveness as per segments. The report also maps the qualitative impact of various market factors on market segments and geographies.

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Cell Therapy And Tissue Engineering Market Size 2020 by Top Leading Companies- BioCardia Betalin Therapeutics, MEDIPOST Co., MaxCyte BioReliance...

IPS Cell Therapy Comments Off on Cell Therapy And Tissue Engineering Market Size 2020 by Top Leading Companies- BioCardia Betalin Therapeutics, MEDIPOST Co., MaxCyte BioReliance… | January 16th, 2020

Stafford Township, NJ Stem cell therapy is an incredible process for healing damaged tissue, so it seems remarkable that it is availablefor petsright here in Manahawkin. Stafford Veterinary Hospital, at 211 North Main St., began offering the advanced treatment in 2019, under the direction of Michael Pride, medical director at the facility.

There, stem cell therapy is most commonly applied to osteoarthritis, but can also be used in dogs suffering from hip dysplasia and ligament and cartilage injuries, as well as mobility ailments and some chronic inflammatory issues such as inflammatory bowel disease and chronic kidney disease, which is common in cats.

Stem cell therapy is actually the only thing that can help to reverse the process of arthritis, Pride said. Everything else is a Band-Aid.

This process can actually help to rebuild cartilage and really reduce inflammation without the need of using aspirin-type medications, Pride said. Its a newer technology that we can use to avoid chronic use of medications, which might actually be detrimental in the long term for the liver or kidneys.

Stem cell therapy treats the source of the problem by offering the ability to replace damaged cells with new ones, instructs the website staffordvet.com.

Stem cells are powerful healing cells in the pets body that can become other types of cells. For example, in the case of arthritis, stem cells can become new cartilage cells and have natural anti-inflammatory properties, thus reducing pain and increasing mobility.

The stem cells are your primary structural cell for all other cells in the body; they can differentiate into almost any other cell, explained Pride. Were processing it down into that primordial stem cell; were activating it, and were injecting it into where it needs to be, and it just starts taking on the characteristics of the cells around it.

Table-top machines from MediVet Biologics are the first Adipose Stem Cell therapy kits for in-clinic use, a major advancement. Stem cell therapy for animals has been commercially available since 2004. MediVet pioneered in-clinic treatment options around 2010.

Pride believes Stafford Veterinary Hospital offers the only such treatment in the immediate area; another is in Egg Harbor Township, Atlantic County.

Were always trying to figure out different ways to help the patient without hurting them, he said while petting a kitten that had been a patient for another type of treatment.

As stem cell therapy is more in the news regarding humans, a pet owners first question might be where the stem cells come from that are used in the process. The answer: from fat tissue of the pet itself, extracted and processed the same day.

As the therapy has been refined in the last decade, it has actually started to become a lot easier, more cost-effective more recently, said Pride, since weve been able to process fat tissue instead of actually getting bone marrow.

Fat tissue actually has a much higher concentration of adult stem cells than bone marrow does, so its less painful for the patient, they heal a lot easier, and we dont have to process it in a different facility.

Everything comes from the animal, and we give it back to the animal. Nothing comes from another animal. We dont have to worry about them rejecting the sample; its their own tissue, and were giving it back to them.

The pet typically goes home the same day after about eight hours. First, X-rays and a consultation with the veterinarian can determine whether the pet is a candidate for the treatment.

A pet owner may not even know that their animal has arthritis.

Cats have a lot of inflammatory issues that they tend to be very good at hiding, said Pride. A lot of people dont realize that they have arthritis. They think, oh, my cats just getting older; hes not jumping as much; hes not as strong; hes just sleeping most of the day, but actually he has arthritis. Its very difficult to diagnose in cats. A lot of times you end up having to do X-rays to find where the arthritic joints happen to be.

An inch-and-a-half incision is the minor surgery that harvests the fat tissue from the belly while the pet is anesthetized. For a cat, about 20 gramsare extracted. For a large dog, about 40 gramsare needed. While the pet is recovering from the incision surgery, the veterinary hospital is processing the sample. When the sample is ready, the pet is sedated because we then have to give them the joint injections. Then we can reverse the sedation, and they go home.

We asked the doctor if the process always works. He gave the example that on average, a dog such as a boxer that was hobbled is now able to walk without seeming like its painful. In an extreme positive case, a dog that had been barely walking might be bouncing all over the place in two months.

It doesnt always work to the extent that we would love it to, but we usually notice that there is a positive effect from it, Pride remarked. Every patient will be different in what they experience.

For the same reason that everyones situation is going to be different, cost of treatment was not given for this story.

It generally takes about 30 to 60 days for relief to show, the veterinarian said, and the animals progress will be monitored.

On average, results last about 18 months to two years before more stem cells might have to be injected. The procedure takes about an hour.

The nice thing is once we collect those stem cells (from the first procedure), we can bank the leftovers they are cryogenically stored at MediVet corporate headquarters in Kentucky and we dont have to go through the initial anesthetic surgery, said Pride.

Stem cell therapy is one of several innovative modalities available at Stafford Veterinary Hospital. Laser therapy, acupuncture and holistic medicine are others. Care for exotic pets is available, as is emergency pet care.

Visit the website staffordvet.com or call 609-597-7571 for more information on general and specialized services, including: vaccinations, microchipping, spayingand neutering, dental care, wellness exams, dermatology, gastrology, oncology, opthalmology, cardiology, soft-tissue surgery, ultrasound, radiography, nutrition, parasite control, boarding, laborand delivery, end-of-life care, and cremation.

Stafford Veterinary Hospital has been in business since 1965, founded by Dr. John Hauge. Today, five highly skilled veterinarians are on staff, and a satellite, Tuckerton Veterinary Clinic, is at 500 North Green St. in Tuckerton.

Pride has been medical director at Stafford Veterinary Hospital since 2008. He attended Rutgers University, then earned his Veterinary of Medicine degree at Oklahoma State University.

The mild-mannered doctor feels a great rewardfrom treating animals that cant speak for themselves when they feel bad.

These guys, theyre always thankful; you can see what they think, he said of treated pets. The turnaround in their attitude, the turnaround in their ability to be more comfortable, you can see it in their faces; you can see it in their actions. You learn to read animals over time.

Its knowing that were helping those who cant help themselves, he added, and you can see it in them; thats the most gratifying.

mariascandale@thesandpaper.net

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Stem Cell Therapy for Dogs and Cats Is Innovative at Stafford Veterinary Hospital - By MARIA SCANDALE - The SandPaper

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