Monthly Archives: April 2022

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Stem Cell Res Ther. 2022 Apr 4;13(1):145. doi: 10.1186/s13287-022-02821-3.

ABSTRACT

BACKGROUND: With the widespread of Coronavirus Disease 2019 pandemic, in spite of the newly emerging vaccines, mutated strains remain a great obstacle to supportive and preventive measures. Coronavirus 19 survivors continue to face great danger of contacting the disease again. As long as no specific treatment has yet to be approved, a great percentage of patients experience real complications, including among others, lung fibrosis. High oxygen inhalation especially for prolonged periods is per se destructive to the lungs. Nevertheless, oxygen remains the first line support for such patients. In the present study we aimed at investigating the role of amniotic fluid-mesenchymal stem cells in preventing versus treating the hyperoxia-induced lung fibrosis in rats.

METHODS: The study was conducted on adult albino rats; 5 pregnant female rats were used as amniotic fluid donors, and 64 male rats were randomly divided into two groups: Control group; where 10 rats were kept in normal atmospheric air then sacrificed after 2 months, and hyperoxia-induced lung fibrosis group, where 54 rats were exposed to hyperoxia (100% oxygen for 6 h/day) in air-tight glass chambers for 1 month, then randomly divided into the following 5 subgroups: Hyperoxia group, cell-free media-treated group, stem cells-prophylactic group, stem cells-treated group and untreated group. Isolation, culture and proliferation of stem cells were done till passage 3. Pulmonary function tests, histological examination of lung tissue under light and electron microscopes, biochemical assessment of oxidative stress, IL-6 and Rho-A levels, and statistical analysis of data were performed. F-test (ANOVA) was used for normally distributed quantitative variables, to compare between more than two groups, and Post Hoc test (Tukey) for pairwise comparisons.

RESULTS: Labelled amniotic fluid-mesenchymal stem cells homed to lung tissue. Stem cells administration in the stem cells-prophylactic group succeeded to maintain pulmonary functions near the normal values with no significant difference between their values and those of the control group. Moreover, histological examination of lung tissues showed that stem cells-prophylactic group were completely protected while stem cells-treated group still showed various degrees of tissue injury, namely; thickened interalveolar septa, atelectasis and interstitial pneumonia. Biochemical studies after stem cells injection also showed decreased levels of RhoA and IL-6 in the prophylactic group and to a lesser extent in the treated group, in addition to increased total antioxidant capacity and decreased malondialdehyde in the stem cells-injected groups.

CONCLUSIONS: Amniotic fluid-mesenchymal stem cells showed promising protective and therapeutic results against hyperoxia-induced lung fibrosis as evaluated physiologically, histologically and biochemically.

PMID:35379329 | DOI:10.1186/s13287-022-02821-3

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Potential effect of amniotic fluid-derived stem cells on hyperoxia-induced pulmonary alveolar injury - DocWire News

Tissues often fail to regenerate from traumatic muscle-loss injuries such as gunshot wounds and car accidents, and new research in mice from the University of Michigan sheds light on why.

The findings suggest new treatment strategies that could eventually restore function and prevent limb loss.

Skeletal muscle is the tissue that defines how we move and communicate, and its able to repair itself after injury through stem cells. But this doesnt happen when significant chunks of muscle are destroyed, known as volumetric muscle loss. Despite the prevalence of these injuries, little is understood about why they consistently overwhelm the bodys natural regenerative processes. And the medical community has no agreed upon standards of care for dealing with them.

In order to understand why volumetric muscle loss injuries do not heal, U-M researchers collaborated with partners at Georgia Tech, Emory University and the University of Oregon to study these injuries in mice.

Different types of white blood cells contribute to the repair of muscle injury by removing debris and signaling to stem cells to coordinate regeneration. However, the new results suggest that immune cells become dysregulated and prevent stem cell repair. For instance, the U-M team found that after volumetric muscle loss injuries that do not heal, neutrophilsa type of white blood cellremain at the injured site longer than normal.

The persistence of neutrophils at the injury site reduces the ability of muscle stem cells to make new and repair existing muscle fibers, said Jacqueline Larouche, a Ph.D. student in biomedical engineering at U-M and first author of the paper in the Proceedings of the National Academy of Sciences.

In addition to the neutrophils not doing their jobs properly, the team also found that they were being killed by other immune cells. Carlos Aguilar, U-M assistant professor of biomedical engineering, called this counterintuitive. Using single-cell RNA sequencing and imaging, neutrophils were observed to communicate with natural killer cells. Those natural killer cells essentially prompted neutrophils to self-destruct. By altering how the two cell types communicate, different healing outcomes are possible.

The fact that natural killer cells are inhibiting inflammation caused by neutrophils is a new role for what they might be doing, Aguilar said.

Alex Smith, a former quarterback in the National Football League, represents one of the best known examples of volumetric muscle loss. During a 2018 game, Smith suffered a gruesome compound fracture, breaking both the tibia and fibula of his right leg. Within days, doctors discovered a rare bacterial infection called necrotizing fasciitis spreading in the wound, and they had to remove a great deal of his muscle tissue. It took 17 surgeries and nearly two years for Smith to return to the fielda miracle recovery according to many.

The team hopes that better treatments could mean that recovery from these injuries is no longer miraculous.

The research was funded by the Congressionally Directed Medical Research program of the U.S. Department of Defense and the Defense Advanced Research Projects Agency.

Study: Neutrophil and natural killer cell imbalances prevent muscle stem cell-mediated regeneration following murine volumetric muscle loss

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Recovery from muscle loss injuries hindered by immune cell conflicts - University of Michigan News

Human stem cells can be rebooted so they morph into completely different cells. Now that this already futuristic method has been leveled up, it sounds even more like something out of science fiction.

This isnt about designing humans like the embryos that could not choose their fate in Brave New World. Reprogramming nave pluripotent stem cells (PSCs) was possible before, but researcher Peter Rugg-Gunn and his team from the Babraham Institutes Epigenetics research program in the U.K. have figured out how to get past some potential glitches. Rugg-Gunn, who led a study recently published in Science Advances, has found out what can further promote reprogramming and even which protein to inhibit so it doesnt get in the way.

Nave pluripotent stem cells can specialize into both embryonic (future embryo) and extraembryonic (future placenta and yolk sac) cell types, he told SYFY WIRE. This makes them hugely exciting and valuable for studying the very early stages of human development.

Pluripotent stem cells can self-replicate and create cells for every type of tissue in the human body. In their nave phase, they can take on the same properties as the cells of an embryo before implantation, including influences on gene expression that are not inherited and come from an outside source. These are known as epigenetic influences. They are also able to do something other pluripotent cells are not capable of, which is form extraembryonic cells. In the absence of pluripotent cells that come straight from an embryo, nave PSCs can also be formed by deleting the identity of specialized cells.

After screening for genes that both promote reprogramming and hold it back, the researchers figured out some reasons many previous reprogramming attempts were not that efficient. Reprogramming needs the epigenetic complex PRC1.3. The process involves so may different signals being fired at cells, trying to tell them what to become, and it is thought that PRC1.3 helps them resist the onslaught of signals. It supposedly keeps them from turning into something else besides nave PSCs by preventing certain genes from switching on.

It surprised us that the building blocks of PRC1.3 changed depending on whether the pluripotent stem cells were in a nave or primed state, said Rugg-Gunn. Before we discovered this, it was thought that PRC1.3 was always formed of the same components.

Some experiments in which PRC 1.3 was removed ended up with cells that fast-forwarded into a specialized cell type instead of rewinding to the nave phase. They have a tendency to turn into nerve cells for some reason. The researchers think that some cells might be making PRC1.3 with different ingredients than others, depending on what they want to specialize in, something that also happens early on in human development. It is possible that this complex protects unspecialized cells in embryos and that things dont always go as planned.

Something going wrong with how PRC1.3 affects stem cells could keep an embryo from developing any further. Another thing found to impede reprogramming is the epigenetic protein HDAC2. When this was blocked, cells could be reprogrammed faster. Both of these insights could be valuable for future treatments of genetic diseases. For example, extraembryonic cells might not sound like a big deal, but Rugg-Gunn thinks they can be morphed into pre-placental cells that can be studied to see why the placenta might not be forming the way it should.

We need to be able to create nave pluripotent stem cells with very high efficiency by reprogramming, he said. The current low efficiency of this step is a major barrier, but now that we have identified some problems, we can try to overcome them.

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You can reprogram cells, kind of like a computer and theyve gotten an upgrade - Syfy

Scientists have discovered a brand-new type of cell hiding inside the delicate, branching passageways of human lungs. The newfound cells play a vital role in keeping the respiratory system functioning properly and could even inspire new treatments to reverse the effects of certain smoking-related diseases, according to a new study.

The cells, known as respiratory airway secretory (RAS) cells, are found in tiny, branching passages known as bronchioles, which are tipped with alveoli, the teensy air sacs that exchange oxygen and carbon dioxide with the bloodstream. The new RAS cells are similar to stem cells "blank canvas" cells that can differentiate into any other type of cell in the body and are capable of repairing damaged alveoli cells and transforming into new ones.

Researchers discovered the RAS cells after becoming increasingly frustrated by the limitations of relying on the lungs of mice as models for the human respiratory system. However, because of certain differences between the two, scientists have struggled to fill some knowledge gaps about human lungs. To get a better understanding of these differences on a cellular level, the team took lung tissue samples from healthy human donors and analyzed the genes within individual cells, which revealed the previously unknown RAS cells.

"It has been known for some time that the airways of the human lung are different than in the mouse," senior author Edward Morrisey, a professor at the Perelman School of Medicine at the University of Pennsylvania who specializes in respiratory systems, told Live Science. "But emerging technologies have only recently allowed us to sample and identify unique cell types."

Related: 10 strangest medical cases of 2021

The team also found RAS cells in ferrets, whose respiratory systems are more similar to humans' than those of mice are. As a result, the researchers suspect that most mammals equal or larger in size are likely to have RAS cells in their lungs, Morrisey said.

RAS cells serve two main functions in the lungs. First, they secrete molecules that maintain the fluid lining along bronchioles, helping to prevent the tiny airways from collapsing and maximizing the efficiency of the lungs. Second, they can act as progenitor cells for alveolar type 2 (AT2) cells, a special type of alveoli that secrete a chemical that is used in part to repair other damaged alveoli. (A progenitor cell is a cell that has the capacity to differentiate into another type of cell, similar to how stem cells differentiate into other cells.)

"RAS cells are what we've termed facultative progenitors," Morrisey said, "which means they act as both progenitor cells and also have important functional roles in maintaining airway health." This means RAS cells play a vital role in maintaining healthy lungs, he added.

The researchers think RAS cells may play a key role in smoking-related diseases, such as chronic obstructive pulmonary disease (COPD). COPD is the result of inflammation of airway passages inside the lungs, which can be caused by smoking and, occasionally, air pollution, according to the Mayo Clinic (opens in new tab). The inflammation of the airways makes it harder for the lungs to properly take in enough oxygen; as a result, COPD has similar symptoms to asthma. COPD can also lead to emphysema, in which alveoli are permanently destroyed, and chronic bronchitis, a long-lasting and intense cough usually accompanied by excess phlegm. Every year, more than 3 million people around the world die from COPD, according to the World Health Organization (opens in new tab).

In theory, RAS cells should prevent, or at least alleviate, the effects of COPD by repairing damaged alveoli. However, the researchers suspect that smoking can damage, or even completely destroy, the new cells, leading to the onset of diseases such as COPD.

Patients who have COPD are often prescribed anti-inflammatory drugs or oxygen therapy to ease their symptoms. However, these are only temporary solutions and do nothing to reverse lung damage. RAS cells could potentially be used to improve treatments or even cure COPD, if researchers can properly harness these cells' regenerative properties.

"We really don't know if this discovery could lead to a potential cure for COPD yet," Morrisey said. "However, since COPD is a disease we know very little about, any new insight should help the field start to think about new therapeutic approaches that could lead to better treatments."

The study was published online March 30 in the journal Nature (opens in new tab).

Originally published on Live Science.

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New part of the body found hiding in the lungs - Livescience.com

Two researchers at the University of Toronto and its hospital partners one a stem cell biologist, the other a global health researcher have been honoured with 2022Canada Gairdner Awards,the countrys most prestigious awards for medical and health science.

John Dickwas recognized with a Gairdner International Awardfor the discovery of leukemic stem cells and later work on the diagnosis and treatment of acute myeloid leukemia. He first received the news fromJanet Rossant,president and scientific director of the Gairdner Foundation, earlier this year.

When Janet called, it was definitely an Oh my gosh moment, said Dick, a professor ofmolecular geneticsat U of Ts Temerty Faculty of Medicine and a senior scientist atPrincess Margaret Cancer Centre, University Health Network.

I recall being asked to sit on an evaluation panel for the Gairdners in the early 1990s, not long after setting up my lab in Toronto. That seemed like the epitome of achievementand I never imagined in my wildest dreams that one day Id receive a Gairdner award.

The John Dirks Canada Gairdner Global Health Award went to Zulfiqar Bhuttafor his research on community-based and policy interventions in child and maternal health, especially among vulnerable populations.

Im very pleased and grateful, said Bhutta, a professor in the departments ofnutritional sciencesandpediatricsat Temerty Medicine and at theDalla Lana School of Public Health, and the director of theCentre for Global Child Healthand a senior scientist at The Hospital for Sick Children.

There are not many awards for research in global or public health, and the Gairdners occupy a special place in Canada and globally, said Bhutta, who moved to Toronto in 2013 and maintains a research group at theAga Khan Universityin Pakistan. It really is a pinnacle and most humbling.

Dick and his lab were the first to discover and describe leukemia stem cells, which can self-renew and drive both cancer growth and relapse after treatment.

Those findings have led to new clinical approaches for acute myeloid leukemia and related blood cancers, and spurred research on the role of stem cells in solid tumours of the colon, breast and brain, among other sites.

Dick said he didnt set out to discover leukemia stem cells, but instead began by plugging away at basic science on the blood system in mice, experimenting with ways to put genes into stem cells.

In a key advance in the late 1980s, Dicks lab developed a way to transplant human blood stem cells into immune-deficient mice. This xenograft assay was a world-firstand enabled Dick and other researchers to track and test the human cells growth and replication, albeit in the living system of the mouse.

At the same time, Dicks lab created the first xenograft models of human leukemiaand developed a method to purify leukemia stem cells, allowing for detailed comparisons of those cells and leukemia cells without stem-like properties.

Most people thought those early experiments wouldnt work, said Dick. But lo and behold some of them worked beautifully, and we were able to characterize leukemia stem cells and non-stem cells. Leukemia is a caricature of normal developmentand we exploited that.

Dick and his team began counting individual cells much likeJames TillandErnest McCullochafter their discovery of stem cells in Toronto in 1961, Dick noted. They made the startling finding that stem cells are extremely rare in acute myeloid leukemia roughly one in a million, in a given population of leukemia cells.

They later found that relapse of acute myeloid leukemia is linked to the survival of leukemia stem cells after therapyand, using patient blood samples, they showed that leukemia stem cells that cause relapse are already present in the blood the day the patient first shows up at the clinic and before therapy begins.

Dicks lab eventually developed a 17-gene stemness score that physicians use to predict patient risk and outcomes, which increasingly helps guide therapeutics. Its a new kind of approach for effective patient-specific intervention, which is gratifying, Dick said.

Dick credits many colleagues for his successes, starting with the trainees in his lab. He said their technical skills and passion were critical, andthat their ideas were often essential.

For most of our findings, no one had the right ideas, Dick said. We just threw our thoughts in a melting pot the good and the bad, and the resulting fusion took us in completely unexpected directions. In that intellectual foment, trainees have contributed so much. Theyve been the best post-docs and graduate students you could imagine.

He also thanked his clinical collaborators at Princess Margaret Cancer Centre and other hospitals, as well as his colleagues at U of T.

Human disease is the best sourcebook for raising and testing research questions, so I needed that constant interchange with clinicians, Dick said. But I benefited hugely from the intellectual rigour and collegiality of my colleagues in molecular genetics. I dont think I could have done this work anywhere but Toronto.

Bhuttas career began in neonatology in Pakistan, but he soon expanded his focus beyond infants.

I realized you cant work with babies without working with mothers and the moment you start working with mothers, you get to social determinants of health, said Bhutta, the first U of T faculty member to win the John Dirks Canada Gairdner Global Health Award.

For more than three decades, Bhuttas research has influenced policy and practice in global child and maternal health through implementation science, research synthesis and trials, as well as studies of malnutrition and obesity, among other approaches.

Ive learned as I went along, but Ive been fortunate to work in a variety of areas, often on large-scale projects, with opportunities to make a difference in the short- and long-term, said Bhutta, who is also affiliated with U of Ts Joannah & Brian Lawson Centre for Child Nutrition.

Bhutta and his colleagues at Aga Khan University provided some of the first scientific evidence on the impact of lady health workers in community-based interventions in Pakistan. The government ofBenazir Bhutto began employing the workers in the mid-1990s, with the goal of reducing child and maternal risk factors and deaths.

Bhutta and his team helped evaluate those interventions in a series of cluster randomized trials a method common in public health that allows researchers to compare program impacts across groups or clusters of people. Among their findings: using chlorhexidine for cord care during home births reduced neonatal infection and death and public-sector community health workers working in rural populations could indeed help reduce perinatal fatalities.

They also showed that when women began to visit health facilities, facility-based births increased. Moreover, they found that womens embrace of the community health system did not falter after the formal period of the intervention ended.

Thats diffusion of innovation, when improvements become ingrained, said Bhutta. People said that women would suffer de-development after the initial intervention, but that did not happen. The lesson was that when you increase capacity around womens health, you can move away and they never look back.

Bhutta and his team provided evidence for expansion of the community-based worker model in Pakistan and countries in the Global South, but their work also highlighted the limits of what those workers can achieve.

You cant do much about a woman who is bleeding to death without access to a facility with a blood bank, Bhutta said. Ive seen many efforts to upgrade community interventions to physician-level care fall flatbecause community workers are not physicians.

Many of those failures were closely linked to social determinants of health, Bhutta said. He recalled that in a Pakistani hospital where his wife worked in the 1990s, pregnant women kept arriving dead at the hospitaldespite living just a few kilometres away. It turned out the delays were often due to an imbalance in decision-making power between males in females,a lack of money for transportor misunderstanding of the severity of the medical crisis.

These problems dont have a biomedical solution, said Bhutta. They need education, womens empowerment, and building social and economic resources at the community level.

Today, Bhutta continues to pursue research on child and maternal health in the Global Southand among marginalized populations in high-income countries. But he is broadening his focus further to address another social determinant of health: climate change.

I would like to work on solutions to climate change for the poorest of poor before countries agree and develop policy, said Bhutta. People are dying nowfrom food shortages and heat shocks. I want to help bring communities together on a self-help basisto promote innovations without the need for external supports. Watch that space.

The Gairdner Foundation was established in 1957 to recognize research that impacts human healthand has since given 402 awards to scientists around the world. About a quarter of those researchers later received Nobel Prizes. The foundation gives seven awards annually. Each recipient receives $100,000and participates in public lectures, research symposia and other outreach events. The foundation is supported by the Government of Canada.

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John Dick and Zulfiqar Bhutta win Canada Gairdner Awards - University of Toronto

Albany NY, United States: Advanced skin closure systems are rapidly being adopted by patients over the last few years, due to advantages such as minimized scarring and improved tolerance of skin. Technological advancements in the adhesive used in skin closure systems have led to improved healing, as these products do not traumatize the edges of surgery site or wound and provide pain-free closure.

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Growing rates of incidence of chronic wounds, rising preference by surgeons for improving patients quality of life, strong emergence of local companies offering skin closure systems at relatively low average selling prices (thereby resulting in reduction in exports and expansion of the domestic market for skin closure systems), and increasing focus by manufacturers on the development of innovative products to reduce the cost burden of post-operative care are some of the factors projected to drive the global skin closure systems market during the forecast period. However, availability of alternative advanced devices for skin closure and increasing pricing pressure in the low-value disposable product segment led by the fragmented market scenario are likely to restrain the global skin closure systems market from 2018 to 2026.

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The global skin closure systems market can be segmented based on product, application, treatment, end-user, and region. In terms of product, the global skin closure systems market can be classified into skin closure strips, sutures & staples, glues, and others. The sutures & staples segment can be sub-divided into sterile and non-sterile. The skin closure strips segment is likely to register a relatively high growth rate during the forecast period, owing to increasing approvals for technologically advanced products that promote non-invasive skin closure. For instance, ZipLine Medical, Inc. announced to have received approval from China Food & Drug Administration (CFDA) for its non-invasive surgical skin closure systems in May 2017. In terms of application, the global skin closure systems market can be bifurcated into invasive skin closure systems and non-invasive skin closure systems. Based on treatment, the market can be divided into surgical skin closure and wound closure. The surgical skin closure segment has been sub-categorized into general surgery, orthopedic surgery, gynecological surgery, cosmetic surgery, and others. Based on end-user, the global skin closure systems market has been classified into long-term care centers, home use, hospitals, clinics, skilled nursing facilities, ambulatory surgical centers, and others. The hospitals segment is projected to dominate the market, in terms of value, from 2018 to 2026, owing to significant improvements in the healthcare infrastructure in developing countries with high growth potential such as China.

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Geographically, the global skin closure systems market has been segmented into five major regions: North America, Europe, Asia Pacific, Latin America, and Middle East & Africa. The market in Asia Pacific is projected to register an above-average growth rate, in terms of value, between 2018 and 2026. This is attributable to significant patient pool suffering from lifestyle-associated disorders such as diabetes and obesity, rise in the demand for affordable and advanced care in the region, and growing inclination of physicians toward adoption of advanced non-invasive skin closure systems in post-surgical and wound care. The skin closure systems market in North America and Europe is developed. The two regions are estimated to hold significant market shares throughout the forecast period, due to increasing focus of major market players to enter the market in these regions. This can be attributed to established reimbursement policies and strong presence of established companies with proper distribution networks in these regions.

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Prominent players operating in the global skin closure systems market are 3M, BSN medical, Chemence Medical, Inc., Ethicon, Inc. (Johnson & Johnson), ZipLine Medical, Inc., Cellpoint Scientific Inc., Smith & Nephew, MicroMend, and Medline Industries Inc.

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This intelligence report by TMR is the outcome of intense study and rigorous assessment of various dynamics shaping the growth of the market. TMR nurtures a close-knit team of analysts, strategists, and industry experts who offer clients tools, methodologies, and frameworks to make smarter decisions. Our objective, insights, and actionable analytics provide CXOs and executives to advance their mission-critical priorities with confidence.

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Skin Closure Systems Market: The skin closure strips segment is likely to register a relatively high growth rate during the forecast period - BioSpace

What Does it Mean for a Global Cure?

By Kambiz Shekdar, Ph.D.

Within the research community, the Holy Grail to cure AIDS had been to find new drugs to Shock and Kill the festering virus from its hiding places (latent infections and viral reservoirs). No such drugs have been developed, yet three persons have been cured using highly imaginative stem cell strategies. The most recent stem cell cure reported in February 2022 is beginning to cause the field to re-think and expand strategies to develop a global cure, including new initiatives by NIH.

HIV INFECTION. The goal of a cure for HIV is to replace human T-cells infected with HIV (left) with non-infected cells (right). Photo credit: Nancy Burson in collaboration with Kunio Nagashima.

Many readers of this newspaper will remember the height of the AIDS epidemic. New York Citys West Village, where this newspaper is based, has always been one of the epicenters of the AIDS epidemic in the United States. The neighborhoods St. Vincents Hospital, now closed, once served as the center for compassionate care of dying patients. Today, an AIDS Memorial sits adjacent to where St. Vincents once stood, as though AIDS is history. In fact, the best way we can memorialize those lost to AIDS and impact the lives and health of future generations to come all around the world is to build a research incubator and hub to accelerate a global cure, right here in New York City.

A brief timeline of 40 years of AIDS: the modern HIV epidemic started in the early 1980s. The first life-saving AIDS drug cocktail was introduced by Dr. David Ho in 1995. Global access to the drugs was initiated by President George W. Bush in 2003 via PEPFAR (Presidents Emergency Plan for AIDS Relief). In 2012, the FDA approved the use of existing AIDS medications to prevent HIV infection. AIDS may have been tamed, but it did not go away; it has been smoldering ever since.

HIV-associated neurocognitive disorders (HAND) occur in some 50% of people living with HIV. HAND is not in the least bit addressable by any of the many existing AIDS medications available today, not even in people who may achieve undetectable viral levels using existing AIDS medications. The disease continues to ravish the poorest and most disenfranchised communities, in the U.S. this started with the gays and now includes black women, our prison populations, trans individuals and our inner cities.

40 million people around the world are living with HIV, making Planet Earth a massive petri dish for the emergence of new strains. COVIDs Delta, Omicron, and Deltacron variants illustrate how infectious agents can change and evade existing defenses. So far, drug makers have been able to develop stronger and newer drugs to new strains of HIV, but this is getting more challenging all the time. Moreover, young gay men in the U.S. have largely stopped using condoms, creating ideal conditions for the spread of any drug-resistant HIV.

With treatment and prevention drugs alone, we can maintain a smoldering HIV/AIDS epidemic, but we cannot end it. With a cure, a vaccine or both, we can end AIDS for good and wipe HIV off the face of the planet.

ENTER CURE: Timothy Ray Brown is the first person cured of AIDS. Mr. Brown recounted how he was cured at a symposium at Columbia University organized by Research Foundation to Cure AIDS. He said that he suffered from both leukemia and AIDS. His physician, Dr. Gero Hutter, had an idea. Dr. Hutter was not an HIV or AIDS specialist, but he recalled from his days in medical school how certain rare individuals are naturally resistant to HIV/AIDS. Mr. Brown needed a bone marrow stem cell transplant to cure his leukemia. What if, Dr. Hutter reasoned, the stem cell transplant was sourced from a donor who is selected from the group of individuals who is naturally resistant to HIV. Could the transplanted stem cells give rise to a new HIV-resistant immune system that would cure Mr. Brown of both AIDS and leukemia? Mr. Brown was a willing guinea pig. The answer to this pairs experiment was a resounding YES!

Who was this leukemia doctor with claims of using stem cells to cure AIDS in 2007, when stem cell science was new and when almost all the experts in the field believed new drugs, not stem cells, were required to achieve a cure? Not even long-time AIDS activists popped any champagne bottles. Was this yet another case of drinking goats milk to cure AIDS? It took years for news of the innovative cure to catch.

DRIP BY MONUMENTAL DRIP, the three cures to date and the new knowledge gleaned from each success have chipped away at the calcified and crusty assumptions with the real-world data and results of what works to cure AIDS. Each of the cures and their contribution to the field of curing AIDS using innovative stem cell strategies are summarized below.

STEM CELL CURE #1, reported in 2007, used HIV resistant stem cells to cure AIDS. But because only one person was cured, it was formally possible that something else or extra about the biology or genetics of either the donor or the patient, or both, was at play. In addition, because the patient suffered from leukemia as well as AIDS, he underwent radiation to eliminate his cancerous immune system first. Also, the donor-derived stem cells that were transplanted into the patient caused a phenomenon known as GVHD (graft versus host disease) where the implanted cells attacked the recipients own cells. Any of these factors could have contributed to the cure of the patient in addition to the curative role of the HIV-resistant stem cell transplant.

STEM CELL CURE #2, reported in 2019, was achieved in much the same way as the first. Now two people were cured, not just one, providing clinical proof that the cure could be repeated and that the first case was not a fluke. Also, by this time, similar cures were attempted in additional patients who suffered with both leukemia and AIDS but using regular stem cell transplants and not HIV-resistant stem cells. All these attempted cures failed, suggesting that radiation to kill off a patients cancerous immune system without adding back HIV resistant stem cells is not sufficient to cure AIDS.

STEM CELL CURE #3, reported in 2022, makes a compelling trifecta. This third was achieved in a multiracial woman. With the first cure being that of a White man, the second that of a Latino male, and the third a multiracial woman, together, the diverse backgrounds of the three individuals cured to date dispels the possibility that any particular biology or genetics of the individuals involved was likely a key factor in achieving any of these cures. Moreover, GVHD did not take hold in patient #3, increasingly pointing to a central curative role being played by the naturally HIV resistant stem cells that were in common across all three cures to date.

Any time when the first patients are cured from a disease that has been lingering for decades, the primary goal of the research community must be to investigate all possible factors, especially all of the factors that were involved in the index cases, that could have contributed to the outcome. 15 years ago, Dr. Hutter showed us all a cure is possible. It took the NIH until the end of 2019 to make its first major announcement prioritizing the development of a global cure for AIDS. Regrettably, the COVID pandemic hit just six weeks later. Since then, I have seen one narrowly-defined call from the NIH for research proposals expressly focused on curing AIDS.

Much more can and must be done to make up for lost time and mobilize a cure. During the last 40 years of living with AIDS, the focus has been on drugs to treat and prevent HIV/AIDS. Now, the cure of three patients using stem cells points to the need to invigorate and add to the field. Room must be made to add new teams that bring novel and differentiated cellular biotechnologies needed to harness natural and curative biological resistance to HIV to develop a global cure.

For full disclosure, I am President and Founder of Research Foundation to Cure AIDS (RFTCA). RFTCA is not about treatment or prevention; were about the cure. Together with our collaboration partners at Columbia University Medical Center, New York Stem Cell Foundation, New York Blood Center and others, RFTCA has applied for NIH grant funding to advance innovate stem cell science originating from The Rockefeller University.

The imaginative and breathtaking results that Dr. Hutter demonstrated when he combined pieces of knowledge known to allbut synthesized by none before himinto a coherent sequence of events that cured AIDS for the first time ever, inspired me ever since I heard about his work. The recent news of the third patient cured of AIDS and how this cure specifically informs the field makes me more hopeful than ever about the prospects of developing a global cure.

Rockefeller University alumnus and biotech inventor Kambiz Shekdar, Ph.D., is the president of Research Foundation to Cure AIDS and Science & LGBTQ editor at WestView News. To support RFTCA, go to https://rftca.org/.

Original post:
World's Third AIDS Patient Cured - WESTVIEW NEWS - WestView News

I want to make sure that by 2025, we have a cost competitive product on the market [on parity with] organic [meat] and we feel very comfortable that we can get there, said Krijn de Nood, who was speaking to FoodNavigator-USA about the ongoing debate over the commercial viability of growing meat from animal cells, at scale, outside of an animal, a technology Impossible Foods founder Dr Pat Brown has dismissed as vaporware.

Asked about last years article in The Counter (drawing upon two techno-economic analyses of cell-cultured meat: CE Delft 2021 andHumbird 2020) arguing that cell-cultured meat faces "intractable technical challenges at food scale, de Nood said: Its always good to read those articles and test your hypotheses and see if you are wrong.

But if we look at our models, both on the scalability trajectory and on the cost reduction trajectory, we feel very comfortable that by 2025, we can go to the market with a price competitive product. The Delft analysis assumed 32 days for the whole process and we can do it - proliferating the cells and then [differentiating] them into muscle and fat cells in less than two weeks.

This also gives us a huge cost advantage from an energy and labor perspective.

While achieving certain cell densities is important, he said, What matters is the biomass accumulation rate. Maybe you can have great cell densities, but if it takes you six weeks to get to them, thats not so efficient, so its one of the reasons we chose iPScs [induced pluripotent stem cells], because they have a faster proliferation rate, they divide faster, so the accumulation of kilograms of meat is faster.

Obviously there's a risk accompanied with scaling up any process, but were not talking about a wild gamble here.

Meatable - which is working with porcine and bovine induced pluripotent stem cells - closed a $47m Series A round (bringing its total funding to $60m) last year, and has just hired former Chr. Hansen president and CEO Cees de Jong as chairman of the board; former Fonterra Europe & Africa president Hans Huistra as COO; and biochemist Jef Pinxteren as VP of development.

At our[pilot-scale]production facility in Delft, we have moved from grams to the kilograms range, so product development can take a big leap, plus for regulatory approval you also need to produce consistent batches, said de Nood.

We have gone from being an R&D company to being a food company.

For commercial launch, he said, Singapore[where cell-cultured meat products, from Eat Just, are already on sale, albeit on a tiny scale]is probably going to be an interesting entry market. After that, we hope that the US will open up for us, as from a market size perspective, its a much more attractive proposition than Singapore, although Singapore is a very good testing market as there are people with a lot of different ethnicities and a willingness to adopt new technologies.

Currently, Meatable is considering asemi-commercialfacility in Singapore, while a larger-scale facility capable of producing 10 kilotons a year would probably be better placed in a larger market such as the US or Europe.

In Europe, said de Nood,the positive thing is that the regulatory landscape is defined[firms must go through the Novel Food Regulation, a pre-market approval process],but it takes a long time, whereas in the US, the process is a work in progress [the FDA says it will publish draft guidance on the pre-market consultation process this year], but seems likely to move more rapidly, he said. "Hopefully months not years.

Meatables first commercial product will be pork, said de Nood. Pork is the most consumed meat globally, especially in Asia, plus there's also a supply demand imbalance right now because of swine fever. But we have also developed a beef line, which is super interesting, especially for Europe and the US our technology is species independent, so at some point we will dofish as well."

He added: Right now what we believe we need for commercial scale is about 10,000 liter bioreactors, but thats only at the beginning, and thats why its so special we have a collaboration with DSM, as they have experience of working with bioreactors on a large scale. DSM also has a lot of experience with taste and texture enhancers[that Meatable can tap into].

Asked about progress on enabling technologies for cell-cultured meat, de Nood said: If you just look at all the growth factors, the amino acids, the minerals that are required, what is very encouraging is that not only startups, but also big corporates are jumping into this, so we have a joint development agreement with DSM, which is really focused on reducing the cost of growth factors[produced via microbial fermentation].

There are several things we can do, so one is moving from pharma to food grade, one is finding other microorganisms to produce these growth factors, and there's also adaptation of the cells so they actually need less. There are a lot of opportunities to really get costs down quite significantly.

So what kinds of products is Meatable working on?

For the first products,said de Nood,we have the two [separate]production lines[for fat and muscle cells]and then we mix them at the end, but we are also working on whole cuts, which account for a huge percentage of the[conventional meat]market, and we are one of the few companies who can actually co-culture cells, so that's exciting stuff.

Asked about scaffolding, he said,We're using a variety of different scaffolds, but its a little bit IP sensitive.

Meatable is effectively reprogramming Hematopoietic stem cells (HSCs) so that they turn into [induced] pluripotent stem cells (iPS cells) or master cells that can differentiate into multiple cells types such as muscle and fat, and proliferate indefinitely.

Induced pluripotent stem cells behave like embryonic stem cells, but dont come from embryos, and dont require the slaughter or harm of any animal, CTO Dan Luining told us when the company emerged from stealth mode in 2018:"The collection method is truly non-invasive. After the calf is born and the umbilical cord is detached, we cannulate one of the veins in the cord and collect the blood in a blood bag. From this blood we isolate cells in the lab."

After that, the blood cells are effectively 'reprogrammed' to a pluripotent state using technologypioneered by Shinya Yamanakas lab in Kyoto, Japan that was awarded the2012 Nobel prize.

Luining added:"The method works by temporarily kickstarting the genes that were active during the state when the animal was only a few cells big. At that moment the cells were in a stage where they could become anything, which we call pluripotent. Professor Yamanaka figured out which genes were active at that time and showed that if you kickstart these genes again the cells behave like pluripotent cells.

"Once started the pluripotent state becomes stable and the cells self-perpetuate this state. These cells have amazing benefits including: unlimited proliferation, complete serum free growth, suspension growth, and pluripotency, the ability to become any cell type that we want.

See the article here:
Meatable CEO weighs into debate over viability of cell-cultured meat: 'What matters is the biomass accumulation rate' - FoodNavigator-USA.com