Study quantified coronary plaque changes in patients administered 4 g/day of VASCEPA® (icosapent ethyl) on top of statin therapy

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VASCEPA® (Icosapent Ethyl) Reported to Impact Vulnerable Coronary Plaque Features in New Analyses of EVAPORATE Study Presented as Late-Breaking...

European Commission approves second indication of Sarclisa® (isatuximab) for relapsed multiple myeloma

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European Commission approves second indication of Sarclisa® (isatuximab) for relapsed multiple myeloma

MARSEILLE, France, April 19, 2021 (GLOBE NEWSWIRE) -- Pursuant to the article L. 233-8 II of the French “Code de Commerce” and the article 223-16 of the French stock-market authorities (Autorité des Marchés Financiers, or “AMF”) General Regulation, Innate Pharma SA (the “Company” – Euronext Paris: FR0010331421 – IPH; Nasdaq: IPHA) releases its total number of shares outstanding as well as its voting rights as at April 1, 2021:

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Number of Shares and Voting Rights of Innate Pharma as of April 1, 2021

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Nicox Provides First Quarter 2021 Business Update and Financial Highlights

ERYTECH Announces Completion of First Cohort in a Phase 1 Investigator Sponsored Trial of Eryaspase in First-Line Pancreatic Cancer

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ERYTECH Announces Completion of First Cohort in a Phase 1 Investigator Sponsored Trial of Eryaspase in First-Line Pancreatic Cancer

From NIH Research Matters

Long-term, or chronic, stress puts people at risk for a variety of health problems. These can include depression and anxiety, as well as problems with digestion and sleep. Chronic stress has also long been linked to hair loss, but the reasons werent well understood.

Hair growth involves three stages. In growth (anagen), strands of hair push through the skin. In degeneration (catagen), hair ceases to grow, and the follicle at the base of the strand shrinks. In rest (telogen), hair falls out and the process can begin again. Hair is among the few tissues that mammals can regenerate throughout their lifetime.

The hair growth cycle is driven by stem cells that reside in the hair follicle. During growth, stem cells divide to become new cells that regenerate hair. In the resting period, the stem cells are inactive. Until now, researchers hadnt determined exactly how chronic stress impaired hair follicle stem cells.

A team led by Dr. Ya-Chieh Hsu of Harvard University studied the underlying mechanisms that link stress and hair loss. The study was supported in part by NIHs National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Results appeared in Nature, on March 4, 2021.

The researchers began by testing the role of the adrenal glands, which produce key stress hormonescorticosterone in rodents and cortisol in humans. Removing the adrenal glands from mice led to rapid cycles of hair regrowth. Hair follicle regeneration didnt slow as these mice grew older, like it did in control mice. Rather, hair follicle stem cells continued to enter the growth phase and regenerate hair follicles throughout the animals lifespans. The team was able to restore the normal hair cycle by feeding the mice corticosterone.

Subjecting mice to mild stress over many weeks increased corticosterone levels and reduced hair growth. Hair follicles remained in an extended resting phase. Together, these findings supported the role of corticosterone in inhibiting hair regrowth.

The scientists next examined how corticosterone affects hair follicle stem cells. They found that the stress hormone was not regulating stem cells directly. By deleting the receptor for corticosterone from different cells, they determined that the hormone acts on a cluster of cells underneath the hair follicle called the dermal papilla.

Further studies revealed that corticosterone prevented the dermal papilla from secreting GAS6, a molecule they showed can activate hair follicle stem cells. Delivering GAS6 into the skin restored hair growth in mice fed corticosterone or undergoing chronic stress.

Last year, findings from Hsus team advanced the understanding of how stress causes gray hair. These results reveal a key pathway involved in hair loss from chronic stress. These findings may also lead to further insights into how stress affects tissue regeneration in other parts of the body.

In the future, the Gas6 pathway could be exploited for its potential in activating stem cells to promote hair growth, says first author Dr. Sekyu Choi of Harvard University. However, further study is needed to understand whether the same mechanism is at work in people.

by Erin Bryant

This research was supported in part by NIA grant R01AG048908.

Reference: Corticosterone inhibits GAS6 to govern hair follicle stem-cell quiescence. Choi S, Zhang B, Ma S, Gonzalez-Celeiro M, Stein D, Jin X, Kim ST, Kang YL, Besnard A, Rezza A, Grisanti L, Buenrostro JD, Rendl M, Nahrendorf M, Sahay A, Hsu YC. Nature. 2021 Mar 31. doi: 10.1038/s41586-021-03417-2. Online ahead of print. PMID: 33790465.

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How stress causes hair loss | National Institute on Aging - National Institute on Aging

In response to emailed questions, Cellino Biotech CEO and Co-founder Dr. Nabiha Saklayen, talked about the formation of the company and its goal to make stem cell therapies more accessible for patients.

Why did you start this company?

I see a huge need to develop a technology platform to enable the manufacture of cell therapies at scale. We recently closed a $16 million seed financing round led by Khosla Ventures and The Engine at MIT, with participation from Humboldt Fund. Cellino is on a mission to make personalized, autologous cell therapies accessible for patients. Stem cell-derived regenerative medicines are poised to cure some of the most challenging diseases within this decade, including Parkinsons, diabetes, and heart disease. Patient-specific cells provide the safest, most effective cures for these indications. However, current autologous processes are not scalable due to extensive manual handling, high variability, and expensive facility overhead. Cellinos vision is to make personalized regenerative medicines viable at large scale for the first time.

How did you meet your co-founders?

Nabiha Saklayen.

I met my co-founder Marinna Madrid in my Ph.D. research group. We had worked together for many years and had a fantastic working relationship. I then met our third co-founder Matthias Wagner through a friend. Matthias had built and run three optical technology companies in the Boston area and was looking to work with a new team. I was thrilled when we decided to launch the startup together at our second meeting. Matthias built the first Cellino hardware systems in what I like to call Matthias garage. In parallel, I was doing hundreds of expert interviews with biologists in academia and industry, and it started to narrow down our potential applications very quickly. Marinna was doing our first experiments with iPSCs. We iterated rapidly on building new versions of the hardware based on the features that were important to industry experts, such as single-cell precision and automation. Its incredible to witness our swift progress as a team.

What specific need or pain point are you seeking to address in healthcare/life sciences?

In general, autologous therapies are safer for patients because they do not require immunosuppression. The next iteration of cell therapies would use patient-specific stem cells banked ahead of time. Anytime a patient needs new cells, such as blood cells, neurons, or skin cells, we would generate them from a stem cell bank.

Today, patient-specific stem cell generation is a manual and artisanal process. A highly skilled scientist sits at a bench, looks at cells by eye, and removes unwanted cells with a pipette tip. Many upcoming clinical trials are using manual processes to produce stem cells for about ten to twenty patients.

At Cellino, we are converging different disciplines to automate this complex process. We use an AI-based laser system comes to remove any unwanted cells. By making stem cells for every human in an automated, scalable way, we are working towards our mission at Cellino to democratize personalized regenerative medicine.

What does your technology do? How does it work?

Cellinos platform combines label-free imaging and high-speed laser editing with machine learning to automate cell reprogramming, expansion, and differentiation in a closed cassette format, enabling thousands of patient samples to be processed in parallel in a single facility.

In general, autologous, patient-specific stem cell-derived therapies do not require immunosuppression and are safer for patients. Today, patient-specific stem cells are made manually, by hand. To scale the stem cell generation process, Cellino converges different disciplines to automate this complex process. We train machine learning algorithms to characterize cells before our AI-based laser system removes any unwanted cells. By making stem cells for every human in an automated, scalable way, our mission at Cellino is to democratize personalized regenerative medicine. Thats why our vision statement is Every human. Every cell.

Whats your background in healthcare? How did you get to where you are today?

When I arrived at Harvard University for my Ph.D. in physics, I wanted to be closer to real-world applications. Biology is inherently complex and beautiful, and I was interested in developing new physics-based tools to engineer cells with precision. During my Ph.D., I invented new ways to edit cells with laser-based nanomaterials. I collaborated with many brilliant biology groups at Harvard, including the Rossi, Scadden, and Church labs. Working closely with them convinced me that lasers offer a superior solution to editing cells with high precision. That realization compelled me to launch Cellino.

Do you have clinical validation for your product?

Our immediate goal for the next year is to show that our platform can produce personalized, high-quality, R&D-grade stem cells for different patients, which has not been established in an automated manner in the regenerative medicine industry so far. There is significant patient-to-patient variability in manual cell processing, which we eliminate with our platform.

Photo: Urupong, Getty Images

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Cellino Biotech developing tech to help scale stem cell therapies - MedCity News

When it comes to Alzheimers versus science, science is on the losing side.

Alzheimers is cruel in the most insidious way. The disorder creeps up in some aging brains, gradually eating away at their ability to think and reason, whittling down their grasp on memories and reality. As the worlds population ages, Alzheimers is rearing its ugly head at a shocking rate. And despite decades of research, we have no treatmentnot to mention a cure.

Too much of a downer? The National Institutes of Health (NIH) agrees. In one of the most ambitious projects in biology, the NIH is corralling Alzheimers and stem cell researchers to come together in the largest genome editing project ever conceived.

The idea is simple: decades of research have found certain genes that seem to increase the chance of Alzheimers and other dementias. The numbers range over hundreds. Figuring out how each connects or influences anotherif at alltakes years of research in individual labs. What if scientists unite, tap into a shared resource, and collectively solve the case of why Alzheimers occurs in the first place?

The initiatives secret weapon is induced pluripotent stem cells, or iPSCs. Similar to most stem cells, they have the ability to transform into anythinga cellular Genie, if you will. iPSCs are reborn from regular adult cells, such as skin cells. When transformed into a brain cell, however, they carry the original genes of their donor, meaning that they harbor the original persons genetic legacyfor example, his or her chance of developing Alzheimers in the first place. What if we introduce Alzheimers-related genes into these reborn stem cells, and watch how they behave?

By studying these iPSCs, we might be able to follow clues that lead to the genetic causes of Alzheimers and other dementiaspaving the road for gene therapies to nip them in the bud.

The iPSC Neurodegenerative Disease Initiative (iNDI) is set to do just that. The project aims to stimulate, accelerate, and support research that will lead to the development of improved treatments and preventions for these diseases, the NIH said. All resulting datasets will be openly shared online, for anyone to mine and interpret.

In plain language? Lets throw all of our new biotech superstarswith CRISPR at the forefrontinto a concerted effort against Alzheimers, to finally gain the upper hand. Its an Avengers, assemble moment towards one of our toughest foesone that seeks to destroy our own minds from within.

Alzheimers disease was first recognized in the early 1900s. Ever since, scientists have strived to find the cause that makes a brain waste away.

The most prominent idea today is the amyloid hypothesis. Imagine a horror movie inside a haunted house with ghosts that gradually intensify in their haunting. Thats the amyloid horrora protein that gradually but silently builds up inside a neuron, the house, eventually stripping it of its normal function and leading to the death of anything inside. Subsequent studies also found other toxic proteins that hang around outside the neuron house that gradually poison the molecular tenants within.

For decades scientists have thought that the best approach to beat these ghosts was an exorcismthat is, to get rid of these toxic proteins. Yet in trial after trial, they failed. The failure rate for Alzheimers treatmentso far, 100 percenthas led some to call treatment efforts a graveyard of dreams.

Its pretty obvious we need new ideas.

A few years ago, two hotshots strolled into town. One is CRISPR, the wunderkind genetic sharpshooter that can snip way, insert, or swap out a gene or two (or more). The other is iPSCs, induced pluripotent stem cells, which are reborn from adult cells through a chemical bath.

The two together can emulate Dementia 2.0 in a dish.

For example, using CRISPR, scientists can easily insert genes related to Alzheimers, or its protection, into an iPSCeither that from a healthy donor, or someone with a high risk of dementia, and observe what happens. A brain cell is like a humming metropolitan area, with proteins and other molecules whizzing around. Adding in a dose of pro-Alzheimers genes, for example, could block up traffic with gunk, leading scientists to figure out how those genes fit into the larger Alzheimers picture. For the movie buffs out there, its like adding into a cell a gene for Godzilla and another for King Kong. You know both could mess things up, but only by watching what happens in a cell can you know for sure.

Individual labs have tried the approach since iPSCs were invented, but theres a problem. Because iPSCs inherit the genetic baseline of a person, it makes it really difficult for scientists in different labs to evaluate whether a gene is causing Alzheimers, or if it was just a fluke because of the donors particular genetic makeup.

The new iNDI plan looks to standardize everything. Using CRISPR, theyll add in more than 100 genes linked to Alzheimers and related dementias into iPSCs from a wide variety of ethnically diverse healthy donors. The result is a huge genome engineering project, leading to an entire library of cloned cells that carry mutations that could lead to Alzheimers.

In other words, rather than studying cells from people with Alzheimers, lets try to give normal, healthy brain cells Alzheimers by injecting them with genes that could contribute to the disorder. If you view genes as software code, then its possible to insert code that potentially drives Alzheimers into those cells through gene editing. Execute the program, and youll be able to observe how the neurons behave.

The project comes in two phases. The first focuses on mass-engineering cells edited with CRISPR. The second is thoroughly analyzing these resulting cells: for example, their genetics, how their genes activate, what sorts of proteins they carry, how those proteins interact, and so on.

By engineering disease-causing mutations in a set of well-characterized, genetically diverse iPSCs, the project is designed to ensure reproducibility of data across laboratories and to explore the effect of natural variation in dementia, said Dr. Bill Skarnes, director of cellular engineering at the Jackson Laboratory, and a leader of the project.

iNDI is the kind of initiative thats only possible with our recent biotech boost. Engineering hundreds of cells related to Alzheimersand to share with scientists globallywas a pipe dream just two decades ago.

To be clear, the project doesnt just generate individual cells. It uses CRISPR to make cell lines, or entire lineages of cells with the Alzheimers gene that can pass on to the next generation. And thats their power: they can be shared with labs around the world, to further hone in on genes that could make the largest impact on the disorder. Phase two of iNDI is even more powerful, in that it digs into the inner workings of these cells to generate a cheat codea sheet of how their genes and proteins behave.

Together, the project does the hard work of building a universe of Alzheimers-related cells, each outfitted with a gene that could make an impact on dementia. These types of integrative analyses are likely to lead to interesting and actionable discoveries that no one approach would be able to learn in isolation, the authors wrote. It provides the best chance at truly understanding Alzheimers and related diseases, and promising treatment possibilities.

Image Credit: Gerd Altmann from Pixabay

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A Massive New Gene Editing Project Is Out to Crush Alzheimer's - Singularity Hub

Are you stressed out? Your skin can show it. Studies show that both acute and chronic stress can exert negative effects on overall skin wellness, as well as exacerbate a number of skin conditions, including psoriasis, eczema, acne, and hair loss.

But its not just a one-way street. Research has also shown that skin and hair follicles contain complex mechanisms to produce their own stress-inducing signals, which can travel to the brain and perpetuate the stress response.

You may already have experienced the connection between the brain and skin. Have you ever gotten so nervous that you started to flush or sweat? If so, you experienced an acute, temporary stress response. But science suggests that repeated exposure to psychological or environmental stressors can have lasting effects on your skin that go far beyond flushing and could even negatively affect your overall well-being.

The brain-skin axis is an interconnected, bidirectional pathway that can translate psychological stress from the brain to the skin and vice versa. Stress triggers the hypothalamus-pituitary-adrenal (HPA) axis, a trio of glands that play key roles in the bodys response to stress. This can cause production of local pro-inflammatory factors, such as cortisol and key hormones in the fight-or-flight stress response called catecholamines, which can direct immune cells from the bloodstream into the skin or stimulate pro-inflammatory skin cells. Mast cells are a key type of pro-inflammatory skin cell in the brain-skin axis; they respond to the hormone cortisol through receptor signaling, and directly contribute to a number of skin conditions, including itch.

Because the skin is constantly exposed to the outside world, it is more susceptible to environmental stressors than any other organ, and can produce stress hormones in response to them. For example, the skin produces stress hormones in response to ultraviolet light and temperature, and sends those signals back to the brain. Thus, psychological stressors can contribute to stressed-out skin, and environmental stressors, via the skin, can contribute to psychological stress, perpetuating the stress cycle.

Psychological stress can also disrupt the epidermal barrier the top of layer of the skin that locks in moisture and protects us from harmful microbes and prolong its repair, according to clinical studies in healthy people. An intact epidermal barrier is essential for healthy skin; when disrupted, it can lead to irritated skin, as well as chronic skin conditions including eczema, psoriasis, or wounds. Psychosocial stress has been directly linked to exacerbation of these conditions in small observational studies. Acne flares have also been linked to stress, although the understanding of this relationship is still evolving.

The negative effects of stress have also been demonstrated in hair. One type of diffuse hair loss, known as telogen effluvium, can be triggered by psychosocial stress, which can inhibit the hair growth phase. Stress has also been linked to hair graying in studies of mice. The research showed that artificial stress stimulated the release of norepinephrine (a type of catecholamine), which depleted pigment-producing stem cells within the hair follicle, resulting in graying.

While reducing stress levels should theoretically help to alleviate damaging effects on the skin, theres only limited data regarding the effectiveness of stress-reducing interventions. There is some evidence that meditation may lower overall catecholamine levels in people who do it regularly. Similarly, meditation and relaxation techniques have been shown to help psoriasis. More studies are needed to show the benefit of these techniques in other skin conditions. Healthy lifestyle habits, including a well-balanced diet and exercise, may also help to regulate stress hormones in the body, which should in turn have positive effects for skin and hair.

If you are experiencing a skin condition related to stress, see a dermatologist for your condition, and try some stress-reducing techniques at home.

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Stress may be getting to your skin, but it's not a one-way street - Harvard Health Blog - Harvard Health

Leukemia cutis can happen when leukemia cells enter your skin. This rare condition causes patches of discolored skin to appear on the body.

In some cases, the appearance of leukemia cutis lesions on the skin is the first sign of leukemia a cancer of the blood and bone marrow.

Along with standard leukemia therapies, this complication can usually be addressed with topical treatments to help heal the damaged skin. If you have leukemia cutis, your outlook will usually depend on your age and the type of leukemia you have.

Leukemia cutis is an uncommon complication, affecting only about 3 percent of people with leukemia. However, it is often a sign that the cancer is at an advanced stage.

With leukemia, malignant leukocytes (white blood cells) are usually only present in the bloodstream. In the case of leukemia cutis, the leukocytes have entered the skin tissue, causing lesions to appear on the outer layer of your skin. The word cutis refers to the skin, or dermis.

Generally, leukemia cutis results in one or more lesions or patches forming on the outer layer of skin. This condition can mean that the leukemia is more advanced and may have spread to your bone marrow and other organs.

Because there are fewer healthy white cells to combat infections caused by other diseases, rashes and sores may be more common among people with leukemia. Low blood platelets from leukemia can cause damage to blood vessels that appear as red spots or lesions on the skin.

These may include:

However, these skin changes are different than those brought on by leukemia cutis.

While the legs are the most common area for leukemia cutis lesions to appear, they can also form on the arms, face, trunk, and scalp. These skin changes can include:

The lesions usually dont hurt. However, with certain types of leukemia particularly acute myeloid leukemia (AML) the lesions may bleed.

A dermatologist may initially diagnose leukemia cutis based on a physical examination of the skin and a review of your medical history. A skin biopsy is needed to confirm the diagnosis.

Leukemia cutis is a sign of leukemia. It wont develop if the body isnt already dealing with this type of blood cancer.

But leukemia isnt just one disease. There are multiple types of leukemia, each one classified by the kind of cell affected by the disease.

You can also have an acute or a chronic form of leukemia. Acute means it comes on suddenly and usually with more severe symptoms. Chronic leukemia develops more slowly and often with milder symptoms.

The types of leukemia that most commonly trigger leukemia cutis are AML and chronic lymphocytic leukemia (CLL).

Scientists arent sure why cancerous leukocytes migrate to skin tissue in some people with leukemia. It may be that the skin is an optimal environment for healthy leukocytes to transform into cancerous cells.

One possible risk factor that has emerged is an abnormality in chromosome 8, which has been found more often in individuals with leukemia cutis than in those without it.

Treating leukemia cutis usually includes treatment for leukemia as the underlying condition.

The standard leukemia treatment is chemotherapy, but other options may be considered depending on your overall health, your age, and the type of leukemia you have.

Other leukemia treatment options include:

For blood cancers, external beam radiation is a typical form of treatment. With this therapy, a focused beam of radiation is delivered outside the body from various angles. The goal is to injure the DNA in cancer cells to stop them from reproducing.

Immunotherapy, a type of biological therapy, uses the bodys own immune system to fight cancer. It is typically given by an injection that either stimulates immune system cells activity or blocks the signals cancer cells send to suppress the immune response.

Immunotherapy may also be given orally, topically, or intravesically (into the bladder).

Stem cell transplantation is more commonly known as a bone marrow transplant. Bone marrow is where blood stem cells develop. Stem cells can become any type of cell.

Through stem cell transplantation, healthy blood stem cells replace stem cells damaged by the cancer or by chemotherapy or radiation therapy. However, not everyone is a good candidate for this treatment.

Only treating the leukemia cutis lesions will not address the underlying disease of leukemia. That means treatments designed to remove or reduce lesions should be done in combination with systemic treatment for leukemia itself.

Treatments for leukemia cutis symptoms can include:

Again, these treatments will only treat the leukemia cutis lesions, but systemic treatment of the leukemia itself will be needed as well.

The length of time leukemia cutis lesions may last depends on many factors, including how well the leukemia itself is responding to treatment. If the leukemia goes into remission, its unlikely more lesions will appear.

With effective treatment, existing lesions could fade. However, other factors, including your age and overall health, can affect how widespread the lesions are and how long they may last.

There are encouraging trends in the treatment of leukemia, but it remains a challenging disease to treat and live with.

For people with AML who dont have leukemia cutis, research suggests that the survival rate at 2 years is about 30 percent. However, the survival rate drops to 6 percent among people with the skin lesions.

A separate study of 1,683 people with AML found that leukemia cutis was associated with a poor prognosis, and that those with AML and leukemia cutis may benefit from more aggressive treatment.

The outlook for people with CLL is better, with about an 83 percent survival rate at 5 years. The presence of leukemia cutis doesnt seem to change that outlook very much, according to a 2019 study.

Leukemia cutis is a rare complication of leukemia. It happens when malignant leukocytes invade the skin and cause lesions on the skins outer surface.

AML and CLL are more often associated with leukemia cutis than other types of leukemia.

While leukemia cutis usually means the leukemia is in an advanced stage, there are treatments for both the cancer and this uncommon side effect that may help extend life and improve its quality.

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Leukemia Cutis: Symptoms and Treatment - Healthline

(The Conversation is an independent and nonprofit source of news, analysis and commentary from academic experts.)

Christopher Tuggle, Iowa State University and Adeline Boettcher, Iowa State University

(THE CONVERSATION) The U.S. Food and Drug Administration requires all new medicines to be tested in animals before use in people. Pigs make better medical research subjects than mice, because they are closer to humans in size, physiology and genetic makeup.

In recent years, our team at Iowa State University has found a way to make pigs an even closer stand-in for humans. We have successfully transferred components of the human immune system into pigs that lack a functional immune system. This breakthrough has the potential to accelerate medical research in many areas, including virus and vaccine research, as well as cancer and stem cell therapeutics.

Existing biomedical models

Severe Combined Immunodeficiency, or SCID, is a genetic condition that causes impaired development of the immune system. People can develop SCID, as dramatized in the 1976 movie The Boy in the Plastic Bubble. Other animals can develop SCID, too, including mice.

Researchers in the 1980s recognized that SCID micecould be implanted with human immune cells for further study. Such mice are called humanized mice and have been optimized over the past 30 years to study many questions relevant to human health.

Mice are the most commonly used animal in biomedical research, but results from mice often do not translate well to human responses, thanks to differences in metabolism, size and divergent cell functions compared with people.

Nonhuman primates are also used for medical research and are certainly closer stand-ins for humans. But using them for this purpose raises numerous ethical considerations. With these concerns in mind, the National Institutes of Health retired most of its chimpanzees from biomedical research in 2013.

Alternative animal models are in demand.

Swine are a viable option for medical research because of their similarities to humans. And with their widespread commercial use, pigs are met with fewer ethical dilemmas than primates. Upwards of 100 million hogs are slaughtered each year for food in the U.S.

Humanizing pigs

In 2012, groups at Iowa State University and Kansas State University, including Jack Dekkers, an expert in animal breeding and genetics, and Raymond Rowland, a specialist in animal diseases, serendipitously discovered a naturally occurring genetic mutation in pigs that caused SCID. We wondered if we could develop these pigs to create a new biomedical model.

Our group has worked for nearly a decade developing and optimizing SCID pigs for applications in biomedical research. In 2018, we achieved a twofold milestone when working with animal physiologist Jason Ross and his lab. Together we developed a more immunocompromised pig than the original SCID pig and successfully humanized it, by transferring cultured human immune stem cells into the livers of developing piglets.

During early fetal development, immune cells develop within the liver, providing an opportunity to introduce human cells. We inject human immune stem cells into fetal pig livers using ultrasound imaging as a guide. As the pig fetus develops, the injected human immune stem cells begin to differentiate or change into other kinds of cells and spread through the pigs body. Once SCID piglets are born, we can detect human immune cells in their blood, liver, spleen and thymus gland. This humanization is what makes them so valuable for testing new medical treatments.

We have found that human ovarian tumors survive and grow in SCID pigs, giving us an opportunity to study ovarian cancer in a new way. Similarly, because human skin survives on SCID pigs, scientists may be able to develop new treatments for skin burns. Other research possibilities are numerous.

Pigs in a bubble

Since our pigs lack essential components of their immune system, they are extremely susceptible to infection and require special housing to help reduce exposure to pathogens.

SCID pigs are raised in bubble biocontainment facilities. Positive pressure rooms, which maintain a higher air pressure than the surrounding environment to keep pathogens out, are coupled with highly filtered air and water. All personnel are required to wear full personal protective equipment. We typically have anywhere from two to 15 SCID pigs and breeding animals at a given time. (Our breeding animals do not have SCID, but they are genetic carriers of the mutation, so their offspring may have SCID.)

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As with any animal research, ethical considerations are always front and center. All our protocols are approved by Iowa State Universitys Institutional Animal Care and Use Committee and are in accordance with The National Institutes of Healths Guide for the Care and Use of Laboratory Animals.

Every day, twice a day, our pigs are checked by expert caretakers who monitor their health status and provide engagement. We have veterinarians on call. If any pigs fall ill, and drug or antibiotic intervention does not improve their condition, the animals are humanely euthanized.

Our goal is to continue optimizing our humanized SCID pigs so they can be more readily available for stem cell therapy testing, as well as research in other areas, including cancer. We hope the development of the SCID pig model will pave the way for advancements in therapeutic testing, with the long-term goal of improving human patient outcomes.

Adeline Boettcher earned her research-based Ph.D. working on the SCID project in 2019.

This article is republished from The Conversation under a Creative Commons license. Read the original article here: https://theconversation.com/were-creating-humanized-pigs-in-our-ultraclean-lab-to-study-human-illnesses-and-treatments-156343.

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We're creating 'humanized pigs' in our ultraclean lab to study human illnesses and treatments - Alton Telegraph

Using blobs of skin cells from frog embryos, scientists have grown creatures unlike anything else on Earth, a new study reports. These microscopic living machines can swim, sweep up debris and heal themselves after a gash.

Scientists often strive to understand the world as it exists, says Jacob Foster, a collective intelligence researcher at UCLA not involved with this research. But the new study, published March 31 in Science Robotics, is part of a liberating moment in the history of science, Foster says. A reorientation towards what is possible.

In a way, the bots were self-made. Scientists removed small clumps of skin stem cells from frog embryos, to see what these cells would do on their own. Separated from their usual spots in a growing frog embryo, the cells organized themselves into balls and grew. About three days later, the clusters, called xenobots, began to swim.

Normally, hairlike structures called cilia on frog skin repel pathogens and spread mucus around. But on the xenobots, cilia allowed them to motor around. That surprising development is a great example of life reusing whats at hand, says study coauthor Michael Levin, a biologist at Tufts University in Medford, Mass.

And that process happens fast. This isnt some sort of effect where evolution has found a new use over hundreds of thousands of years, Levin says. This happens in front of your eyes within two or three days.

Xenobots have no nerve cells and no brains. Yet xenobots each about half a millimeter wide can swim through very thin tubes and traverse curvy mazes. When put into an arena littered with small particles of iron oxide, the xenobots can sweep the debris into piles. Xenobots can even heal themselves; after being cut, the bots zipper themselves back into their spherical shapes.

Scientists are still working out the basics of xenobot life. The creatures can live for about 10 days without food. When fed sugar, xenobots can live longer (though they dont keep growing). Weve grown them for over four months in the lab, says study coauthor Doug Blackiston, also at Tufts. They do really interesting things if you grow them, including forming strange balloon-like shapes.

Its not yet clear what sorts of jobs these xenobots might do, if any. Cleaning up waterways, arteries or other small spaces comes to mind, the researchers say. More broadly, these organisms may hold lessons about how bodies are built, Levin says.

With the advent of new organisms comes ethical issues, cautions Kobi Leins, a digital ethics researcher at the University of Melbourne in Australia. Scientists like to make things, and dont necessarily think about what the repercussions are, she says. More conversations about unintended consequences are needed, she says.

Levin agrees. The small xenobots are fascinating in their own rights, he says, but they raise bigger questions, and bigger possibilities. Its finding a whole galaxy of weird new things.

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Frog skin cells turned themselves into living machines - Science News Magazine

Last year, something new was grafted to the tree of life.

Somewhere between a living organism and a robot, these tiny, living machines were created from clumps of stem cells from the African clawed frog. Stem cells from the heart gave them muscle, while skin stem cells provided structure.

Dubbed "Xenobots" (after the frog's scientific name not, alas, xenomorphs), their creators found that the living machines that could complete simple tasks in Petri dishes, as Freethink's Amanda Winkler explained last year.

Those same researchers, from Tufts and the University of Vermont, have now developed a second iteration, Xenobots 2.0, if you will, which can "self-assemble a body from single cells, do not require muscle cells to move, and even demonstrate the capability of recordable memory," as Tufts Now explains.

These Xenobots are also faster, can make their way through more complex environments, live longer than their predecessors, work in concert, and heal themselves.

Yeah, that sounds a lot like the T-1000 to me, too.

First generation Xenobots were constructed with a "top-down" approach, as Tufts put it. The researchers manually placed and surgically sculpted the heart and skin cells to form tiny biological robots in a variety of shapes.

Their shapes chosen with the help of a digital Xenobots simulator then impacted their various movements.

The original Xenobots were capable of "crawling, traveling in circles, moving small objects or even joining with other organic bots to collectively perform tasks," Winkler reported.

But to create Xenobots 2.0, the researchers utilized a "bottom up" approach, published in the journal Science Robotics.

Rather than crafting the frog heart and stem cells, the researchers simply scraped off some skin stem cells from frog embryos. Left to their own devices, the cells glommed together into spheroids on their own.

They could survive for 10 days without food and even grow if some sugar's in the mix.

"We've grown them for over four months in the lab," Tufts' Doug Blackiston, study coauthor, told Science News. "They do really interesting things if you grow them," including forming new, balloon-like shapes.

Some of the cells adapted to grow cilia a few days in. Usually used by cells to push away pathogens and ensure a nice coating of protective mucus, the Xenobots used their cilia to move around, eliminating the need for heart stem cells.

It's an example of life's remarkable plasticity, the researchers say.

"In a frog embryo, cells cooperate to create a tadpole. Here, removed from that context, we see that cells can re-purpose their genetically encoded hardware, like cilia, for new functions such as locomotion," Michael Levin, professor of biology and director of Tufts' Allen Discovery Center and study corresponding author told Tufts Now.

"It is amazing that cells can spontaneously take on new roles and create new body plans and behaviors without long periods of evolutionary selection for those features."

Along with those new body plans came new abilities. Xenobots 2.0 can move around just like the first iteration did, but they are faster than what the researchers constructed. They're also better at sweeping up junk a swarm of them can round up iron oxide particles in a Petri dish and they can coat flat surfaces and shimmy through narrow capillaries.

Because they are biological, the Xenobots could also heal themselves, forming back together after injury even recovering from full-length lacerations halfway through their "bodies" in just 5 minutes.

"In a frog embryo, cells cooperate to create a tadpole. Here, removed from that context, we see that cells can re-purpose their genetically encoded hardware, like cilia, for new functions such as locomotion."

Just like before, the Tufts team turned to computer simulations to tease out the best Xenobot layouts. Researchers at the University of Vermont did the data crunching, using the Vermont Advanced Computing Core's supercomputer cluster, called Deep Green.

Deep Green comes in because "it's not at all obvious for people what a successful design should look like," UVM computer scientist and robotics expert Josh Bongard told Tufts Now. "That's where the supercomputer comes in and searches over the space of all possible Xenobot swarms to find the swarm that does the job best."

The hope is that eventually Xenobots will be able to perform tasks like clearing microplastics from the ocean, or decontaminating soil.

Performing those jobs would be a hell of a lot easier with the ability to retain and access memory for guiding their actions something the original Xenobots lacked. This time around, the researchers gave them the ability to hold on to one piece of information.

The researchers injected the frog stem cells with mRNA carrying the instructions for a protein called EosFP. This protein normally glows green, but when exposed to a specific wavelength of light, it turns red instead.

Armed with their little running light, the Xenobots could now keep a record of being exposed to certain wavelengths of blue light in their environment. Further work could potentially allow them to keep track of multiple variables, or even alter their behaviors accordingly.

"When we bring in more capabilities to the bots, we can use the computer simulations to design them with more complex behaviors and the ability to carry out more elaborate tasks," Bongard said. "We could potentially design them not only to report conditions in their environment but also to modify and repair conditions in their environment."

The researchers' original work already opened questions of what, exactly, Xenobots are. Are they lifeforms? Robots, but made of biological material, in lieu of nuts and bolts?

As you can imagine, these improved iterations which organize on their own are provoking more of the same.

Tel Aviv University evolutionary biologist Eva Jablonka, who is unaffiliated with the work, told Quanta Magazine that she considers them a new form of life "defined by what it does rather than to what it belongs developmentally and evolutionarily."

Armed with a special protein that changes color from green to red, the next generation Xenobots could keep a simple record of their exposure to blue light. Credit: Doug Blackiston & Emma Lederer, Tufts University

University of Melbourne digital ethics researcher Kobi Leins believes new ethical issues arise with the creation of new forms of life. "Scientists like to make things, and don't necessarily think about what the repercussions are," she told Science News.

(For what it's worth, Levin agrees, telling Science News the questions raised by the Xenobots are like "finding a whole galaxy of weird new things.")

Levin hopes that within that galaxy, the Xenobots will do more than perform tasks: they may help us understand how biological life itself develops.

We'd love to hear from you! If you have a comment about this article or if you have a tip for a future Freethink story, please email us at [emailprotected]

Excerpt from:
The Next Generation of Living Machines: Xenobots 2.0 - Freethink

Newswise March 30, 2021 As cancer survival rates improve, more people are living with the aftereffects of cancer treatment. For some patients, these issues include chronic radiation-induced skin injury which can lead to potentially severe cosmetic and functional problems.

Recent studies suggest a promising new approach in these cases, using fat grafting procedures to unleash the healing and regenerative power of the body's natural adipose stem cells (ASCs). "Preliminary evidence suggests that fat grafting can make skin feel and look healthier, restore lost soft tissue volume, and help alleviate pain and fibrosis in patients with radiation-induced skin injury after cancer treatment," says J. Peter Rubin, MD, MBA, FACS, American Society of Plastic Surgeons (ASPS) President-Elect and Chair of the Department of Plastic Surgery at University of Pittsburgh Medical Center. He is one of the authors of a new review of the clinical evidence on fat grafting for radiation-induced skin and soft tissue injury.

"But while promising, available research has some key weaknesses that make it difficult for us to determine the true benefits of fat grafting right now," Dr. Rubin adds. The review appears in the April issue of Plastic and Reconstructive Surgery, the official medical journal of the ASPS.

More than half of patients diagnosed with cancer receive radiation therapy. Because skin cells turn over rapidly, they are exquisitely sensitive to the damaging effects of radiation. In the first few months after treatment, many patients develop acute radiation injury with skin inflammation, peeling, swelling, pain and itching. In most cases, symptoms resolve over time. However, if inflammation continues, radiation-induced skin injury can become a chronic problem leading to tight, stiff skin (fibrosis) with a risk of poor wound healing, ulcers, and tissue loss.

Fat grafting procedures transferring the patient's own fat cells from one part of the body to another have become widely used in many cosmetic and reconstructive plastic surgery procedures. In their review, Dr. Rubin and colleagues round up promising research on fat grafting for patients with radiation-induced skin injury.

In studies of breast cancer patients, fat grafting procedures have reduced pain and other symptoms of radiation-induced skin injury backed up by more-normal cellular appearance of skin cells under the microscope. In other studies, fat grafting has led to reduced risks and better outcomes of breast reconstruction after mastectomy.

For patients with radiation-induced skin injury after treatment for head and neck cancer, fat grafting has led to improvements in voice, breathing, swallowing, and movement. Good outcomes have also been reported in patients with radiation-induced skin injury in the area around the eye or in the limbs.

"The good news is fat grafting has the potential to really help patients with discomfort and disability caused by radiation-induced skin damage," according to Dr. Rubin. While research is ongoing, the benefits of fat grafting seem to result from the wide-ranging effects of ASCs including anti-scarring, antioxidant, immune-modulating, regenerative, and other actions.

"However," he adds, "the available evidence has a lot of shortcomings, including small sample sizes, lower-quality research designs, and a lack of comparison groups." Variations in fat cell collection and processing, as well as the timing and "dose" of fat grafting, make it difficult to compare results between studies. There are also unanswered questions regarding potential risks related to ASC injection and concerns that fat grafting might affect cancer follow-up.

The reviewers outline some steps for further research to clarify the benefits of fat grafting for radiation-induced skin and soft issue injury, including approaches to clinical assessment and imaging studies, testing of skin biomechanics and circulation, and cellular-level analyses. For all of these outcomes, standardized measures are needed to achieve more comparable results between studies.

"We hope our review will inform efforts to establish the benefits of specific types of fat grafting procedures in specific groups of patients," says Dr. Rubin. "To do that, we'll need studies including larger numbers of patients, adequate control groups, and consistent use of objective outcome measures."

Click here to read Fat Grafting in Radiation-Induced Soft-Tissue Injury: A Narrative Review of the Clinical Evidence and Implications for Future Studies.

DOI: 10.1097/PRS.0000000000007705

###

Plastic and Reconstructive Surgery is published in the Lippincott portfolio by Wolters Kluwer.

About Plastic and Reconstructive Surgery

For more than 70 years, Plastic and Reconstructive Surgery (http://www.prsjournal.com/) has been the one consistently excellent reference for every specialist who uses plastic surgery techniques or works in conjunction with a plastic surgeon. The official journal of the American Society of Plastic Surgeons, Plastic and Reconstructive Surgery brings subscribers up-to-the-minute reports on the latest techniques and follow-up for all areas of plastic and reconstructive surgery, including breast reconstruction, experimental studies, maxillofacial reconstruction, hand and microsurgery, burn repair and cosmetic surgery, as well as news on medico-legal issues.

About ASPS

The American Society of Plastic Surgeons is the largest organization of board-certified plastic surgeons in the world. Representing more than 7,000 physician members, the society is recognized as a leading authority and information source on cosmetic and reconstructive plastic surgery. ASPS comprises more than 94 percent of all board-certified plastic surgeons in the United States. Founded in 1931, the society represents physicians certified by The American Board of Plastic Surgery or The Royal College of Physicians and Surgeons of Canada.

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Wolters Kluwer (WKL) is a global leader in professional information, software solutions, and services for the clinicians, nurses, accountants, lawyers, and tax, finance, audit, risk, compliance, and regulatory sectors. We help our customers make critical decisions every day by providing expert solutions that combine deep domain knowledge with advanced technology and services.

Wolters Kluwer reported 2019 annual revenues of 4.6 billion. The group serves customers in over 180 countries, maintains operations in over 40 countries, and employs approximately 19,000 people worldwide. The company is headquartered in Alphen aan den Rijn, the Netherlands.

Wolters Kluwer provides trusted clinical technology and evidence-based solutions that engage clinicians, patients, researchers and students with advanced clinical decision support, learning and research and clinical intelligence. For more information about our solutions, visit https://www.wolterskluwer.com/en/healthand follow us onLinkedInand Twitter@WKHealth.

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Fat grafting shows promise for cancer patients with radiation-induced skin injury - Newswise

The Augustinus Bader story hasbecome a beauty legend. Professor Bader, one of the worlds leading stem-cell experts, makes a groundbreaking wound gel that rehabilitates the skin of burns victims,without the need for grafts or scarring. At a dinner hosted by Robert Friedland, the self-made billionaire and long-time mentor to Steve Jobs, Bader meets Charles Rosier, a young French financier. They are kicking around ideas forfunding the necessary clinical trials forthe product, which would likely run intothetens of millions. Pharmaceutical companies arent interested because most burns victims are in emerging countries, where the market for sophisticated healing products is negligible.

Rosier has a flash of inspiration: couldBader use what he knows about wound healing to make an anti-ageing cream? Yes, answers Bader unhesitatingly. Two years and much cajoling later, the professor makes a prototype skincare cream, and pretty soon anyone who has ever had more than a passing interest in face cream is talking about it.

According to Deloitte, as many as 90per cent of beauty launches fail within ayear. By contrast, the Augustinus Bader skincare brand has grown from a turnover of $7m in 2018 to $70m in 2020. It has also shattered traditional conventions of luxury skincare along the way. For a start, the company launched with just two face products, The Cream (fornormal/oily skin) and The Rich Cream (dry skin) and insisted that apart from cleanser andSPF theyre all you need to use. No eye cream, no neck cream, no serum underneath, no primer ontop just one cream, and a very specific two pumps at that. This was intriguing. Most luxury-skincare brands (the creams retail at205 each) dont just sell you a dream they sell you a regime.

Charles Rosier believes that their inexperience in the beauty industry helpedat first. If Id known how complex and competitive the industry is, maybe Iwouldnt have had so much passion for it. But because I had seen what Augustinuss science could do, I was truly convinced thathe could create a product that was new, disruptive and of higher quality than whatever else was in the market.

As it turned out, it was. Celebrities normally paid handsomely to endorse beauty brands were not only recommending the Augustinus Bader cream unprompted butinvesting in the company too (Courteney Cox, Melanie Griffith and Carla Bruni to note). Usually cynical beauty editors discussed it with the fervour of addicts (myself included). And in February, a panel of more than 300 industry experts voted The Cream and The Rich Cream as Womens Wear Dailys Greatest Skincare Product ofAll Time (Crme de la Mer, launched in 1965, took second place and Este Lauder Advanced Night Repair, from 1982, took third), neatly capping off a pleasing statistic of 36 awards in 36 months.

Bader a softly spoken, bow tie-wearing 61-year-old German is both asthrilled and bemused by the brands success as youd hope. Before making the face cream, he says, he had never used a skincare product in his life. But he likes the fact that now, when he uses the cream before shaving, he no longer cuts himself. It would never have occurred to him to have created a cleanse/tone/moisturise-type regime. Beauty is always from inside, he says. You dont need a routine, as many people have been used to. The idea is that just after washing your face, you use The Cream or The Rich Cream. Everything is in that one product.

Before making the face cream, Bader had never used a skincare product inhis life

It would be tempting to paint Bader asthe sneery scientist, dabbling with the beauty world as a means to an end(close to10per cent of the brands profits in 201920 went to wound-healing research and other charities). The opposite is true: what finally convinced him to embark onthe project was his patients reaction tohisearly prototype: When I gave theproduct to patients with diabetic wounds, their skin became healthier-looking and stronger, and I could see how happy it made them...so for me, even though it was just a skincare product, it developed a kind of medical meaning.

Also subversive is the brandsconspicuous lack ofmiracle ingredients. Baderswork is guided by theprinciple that your skin contains all it needs already its the communication between thecells thats important, notapplying endlessnew ingredients that your skin doesnt recognise. Conventional medicine very often tries to helpby treating symptoms, but what the patientreally wants is a healing process, he says. The creams themselves contain a complex called TCF8, which hesays is mainly made out of vitamins, amino acids and lipid structures.

$70mThe brands turnoverin2020

10%The profits in 20192020 thatwent towards wound-healing research and other charities

11The number of products in the Augustinus Bader line

50%The acceleration in healing time experienced by patientsusing Baders wound-healing gel

According to Charles Rosier, Bader isprobably the person in the team who is strictest about only using gentle ingredients which means the brand is able to satisfy the current appetite for clean skincare too. Thats why theres no SPF; because Bader is vehemently opposed to chemical sun filters and has so far found it hard to make sufficiently premium-feeling sun protection without them. And, says Bader, a little bit of sun is good for your skin as is a little bit of stress (and carrot juice: he says that people who eat a lot of carrots generally have good skin).

Last month the brand also launched avegan version of The Rich Cream, with original ingredients such as beeswax and lanolin removed and a slightly upgraded formulation. It has the same rich texture and the same uncanny ability which fans can eulogise about for hours to hug your skin within seconds of applying.

But is it getting harder to avoid the pull of the beauty mainstream? Some devotees have taken a recent spate of new launches to mean that the brand is moving away from its original one cream is all you need philosophy, and that as a result has lost some of its outsider charm. In the second half of 2020, launches came thick and fast: theres now anEssence, Face Oil, Cleansing Balm, Cleansing Gel and Lip Balm, plus body oils and lotions.

Rosier points outthat most of their competitors have around 200 products and that last years bottleneck of launches was largely due to hold-ups in the lab, as well as Covid-19. Perhaps our philosophy has switched a little from Well give you one cream to Wellgive you the essential basics of a skincare routine, he concedes. Well never do 20 serums, but well do products where we feel they can be better than otherthings that exist in the market, and allow you to have an Augustinus Bader routine and not have to mix our products with other brands.

Given how feverish the current Baderobsession is, it seems unlikely thatcustomers would need much convincingnot to mix other brands products into their routines. What isdebatable is how long this brand can remain a disrupter. Ever the renegade, Bader is less interested in being a beauty outsider than encouraging the rest of the field toraise its game.

This new beauty side of mywork is interesting because, ultimately, healthy skin contributes to beauty and for me, thats notsomething superficial, its something absolutely relevant to all the work that I do, including the medical research. In a way, Ihope that perhaps what we can do is be a little bit game-changing about what a skincare product may want to achieve. And that, to me, sounds like real hope in a jar.

Original post:
Augustinus Bader and the making of a $70m phenomenon - Financial Times

Published on April 2, 2021

Recently, a 43-year-old man was presented at Fortis Hospital, Noida, complaining of severe back pain. Upon investigation, it was found that he was suffering from a rare disease, multiple myeloma which is a type of cancer that forms in the white blood cells or plasma cells. Here cancerous plasma cells accumulate in the bone marrow and crowd around the healthy blood cell that help in fighting infections by building antibodies, this puts the patients life at high risk. He therefore urgently required a Bone Marrow Transplant (BMT). Dr Rahul Bhargava, Director and Head, Hematology and Bone Marrow Transplant, Fortis Hospital, Noida and his team took a timely decision to go ahead with BMT to save his life.

A bone marrow transplant is a procedure to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Bone marrow is the soft, fatty tissue inside your bones. The bone marrow produces blood cells. Stem cells are immature cells in the bone marrow that give rise to different blood cells. Bone marrow transplant has now revolutionised. It is like a peripheral blood stem cell transplant, meaning, it is just like a blood transfusion (like platelet apheresis) which does not require any anesthesia.

Upon further investigation it was revealed that chemotherapy was required before BMT. Following the chemotherapy, on the 10thday of admission the team of doctors engulfed stem cells in the patients body which provided the body with a new source of healthy cells. Safe hospital environment and the doctors expertise in the area ensured that the BMT was done smoothly, without any complications and within 15 days the patient had been discharged. Usually, a patient takes 25-30 days to recover but here, due to patients will to recover and the facilities provided to him in the hospital he recovered at a faster pace.

Dr Rahul Bhargava, Director and Head, Hematology and Bone Marrow Transplant, Fortis Hospital, Noida, said,The case was complicated as the patient was suffering from high-risk multiple myeloma, which is a rare form of cancer. We took the necessary precautions and performed chemotherapy first to which he responded well and post that a Bone Marrow Transplant (BMT) was performed successfully. The process was smooth, and no complications arose during the same. We request patients to not fear BMT and undergo the process when required.

Talking about the clinical excellence at Fortis Hospital, NOIDA,Mr Hardeep Singh, Zonal Director, Fortis Hospital, Noidasaid, The team at Fortis Hospital, Noida try their best to save lives and do not give up even if there is 1% chance of survival. The patient was suffering from high-risk multiple myeloma for which immediate bone marrow transplant was required. The case was managed extremely well and with a lot of patience by Dr Rahul Bhargava and his team. I applaud the team of doctors for their continued commitment towards clinical expertise and patient care.

Original post:
Timely Bone Marrow Transplant by Fortis gives new lease of life to a patient with Multiple Myeloma - APN News

Advances in the treatment of patients with leukemias and lymphomas have led to a significant improvement in survival, which has increased the need for bone marrow transplant as a later-line therapy, said Mehrdad Abedi, MD, who added that Orca-T, a high precision cell therapy, confers significant antitumor activity, minimizes the incidence of acute and chronic graft-vs-host disease (GVHD), and causes less adverse effects (AEs) compared with standard bone marrow transplant among these patients.

There is a lot of research [ongoing]; the holy grail of research is trying to figure out whether we can separate the graft-vs-leukemia or graft-vs-lymphoma effect from GVHD, said Abedi. [The Orca-T trial] is basically looking at the past 10 years of research in this area to try to identify the cells that are good from those that are bad.

During the 2021 Transplantation and Cellular Therapy (TCT) Meetings, findings from an analysis of 2 studies demonstrated a significant reduction in cases of GVHD, a higher GVHD relapse-free survival rate, and a lack of treatment-related mortalities with Orca-T when historically compared with hematopoietic stem cell transplant (HSCT).

Additionally, the median time to neutrophil engraftment, median time to platelet engraftment, and median time from day 0 to hospital discharge was shortened with Orca-T compared with HSCT.

In an interview with OncLive during the 2021 TCT Meetings, Abedi, a professor of cancer, hematology/oncology, and internal medicine in the Department of Internal Medicine, Division of Hematology and Oncology at the UC Davis Comprehensive Cancer Center, discussed the challenges of standard transplant, how Orca-T could overcome some of those limitations, and the potential future of transplant in hematologic malignancies.

Abedi: HSCT has been around for more than 50 years in one form or another. It has been used mostly for patients with blood cancers, [such as] leukemia and lymphoma. Allogeneic bone marrow transplants, where we use cells from a donor, are very effective. [They are associated with] a very high response rate for patients who have no other options and whose disease is going to [recur] without transplant.

The problem [with allogeneic bone marrow transplant] is that it [is associated with] AEs. When we give donor cells to patients after high-dose chemotherapy, [which is given] so that the patients body doesnt reject [the cells], even though the cells are a match for the patient, they can still [develop] severe GVHD.

The acute form of GVHD can be life threatening, whereas the chronic form can become a nuisance for the rest of a patients life. A lot of patients suffer [from GVHD] to the point where they regret going through transplant. Fortunately, that is not everybody, but it is still a problem that needs to be solved and an unmet need for the field.

This research has been focused on [the question of]: Are there specific cells in the graft we give to the patients immune cells that can cause GVHD? Can we separate those cells from those that are responsible for causing graft-vs-leukemia effects?

Basically, Orca Bio approached UC Davis a few years ago to [start] collaborative research with our Good Manufacturing Practice [GMP] facility and to produce these products.

Each graft of [the Orca-T] product has stem cells and immune cells in it. The stem cells are what we need to maintain the graft and [allow the product to] stay in the patient for a long time. The immune cells are the ones that can cause graft-vs-leukemia [effects], which is what we want.

From the work that Robert Negrin, [MD] at Stanford University and many other investigators [did], it is very clear that there is a population of T cells called T-regulatory cells that can prevent GVHD. There are other populations, such as the nave T cells or conventional T cells that can cause GVHD. It looks like a smaller number of [those cells] may actually be helpful; they can cause graft-vs-leukemia, but not GVHD.

The graft is basically designed so that we can give stem cells, but they get rid of a lot of conventional T cells that can cause rapid GVHD. [The graft provides] a small amount of conventional T cells that can cause graft-vs-leukemia effects, as well as the regulatory T cells that can prevent GVHD. UC Davis got involved [with this work] because we have a very robust GMP facility. We helped Orca Bio design these protocols and manufacture the cells. Now, [Orca Bio] has moved on to their own facility. I have been involved [with this research] for the past few years.

[We] havent looked at the QOL data, but there have been several short-term and long-term benefits so far that we have seen.

We give high-dose chemotherapy that can get rid of all [the patients] stem cells and leukemia or lymphoma cells. Then, we give the graft; however, after the graft is given, it takes a couple of weeks usually to engraft [before] new cells [develop]. In between, the patients are sick because of the effects of the chemotherapy; patients also have low blood counts.

[With Orca-T] we have seen that the engrafting [occurs] a little bit earlier. For everyday [sooner] the engraftment [occurs], there is less risk of complication and suffering for the patient. That has been a major difference [with Orca-T].

Also, we have noticed that patients in general are doing better [with Orca-T compared with traditional transplant]. When we give high-dose chemotherapy, it is the same whether the patient is on a clinical trial or not. They may still get sick [with Orca-T] because of the effects of chemotherapy.

However, there is also inflammation [that can occur] as the donor cells are trying to establish themselves in the body because some of them attack the body. That inflammation also adds to the problems with chemotherapy. We havent seen that inflammation [with Orca-T]. We have seen some effects from the chemotherapy, but because we dont have the inflammation, other AEs that we see with the standard of care arent seen with Orca-T.

In general, patients do better [with Orca-T vs standard of care], and that has been a universal experience with all of our patients who have gone through the trial so far.

[Patients] just look and feel better. When they are discharged, they are not as sick compared with patients [receiving] the standard of care.

With the standard of care, after we give the graft, we have to give patients a new medication to prevent GVHD because it is such a lethal problem. If we dont put patients on immunosuppressive medications to prevent GVHD, there is a very high chance that they get and die from GVHD. Those immunosuppressive medications are critical.

The way the Orca-T graft is designed is that we dont need as many of those [immunosuppressive] medications. For example, there is a medication called methotrexate that we give on days 1, 3, 6, and 11 after [standard] transplant. That medication can cause a lot of other AEs, such as mouth sores, delayed engraftment, and kidney [problems], that can make the patient miserable. With Orca-T, we dont have to [give methotrexate], which by itself is a huge improvement.

We do give immunosuppressive medications, such as tacrolimus [Envarsus XR] or sirolimus [Rapamune] to these patients, but we dont give 2 or 3 medications as we usually do with the standard of care. Less immunosuppressive medications mean probably less infection, but more importantly, less AEs. Thats [a factor that has made] a big difference in patient experience.

That is a very loaded question. There are a lot of new drugs coming, some of which are very targeted to treat leukemia or lymphoma. Thus far, we havent seen any curative [benefit] with those drugs, so in most situations, we will still need an allogeneic stem cell transplant for patients.

The exceptions [to that] were rare diseases, such as chronic myeloid leukemia [CML], where [an oral medication was approved] and we dont need to transplant patients. That is an example of a targeted treatment that may exclude [the need to] transplant patients. That would be great because transplant is not a trivial procedure and it has a lot of AEs.

However, [CML] is a very specific disease with 1 gene that causes the disease. In most leukemias and lymphomas, multiple genes are involved, so we dont think single-target treatments will get rid of the disease. We still think that allogeneic transplant will be around for a long time.

In fact, if you look at any center in the country, the volume of transplant has substantially increased over time because patients are living longer. Patients end up being able to go to a transplant vs before when many were dying in the middle of their treatment and not getting to transplant.

That being said, there are 2 directions [we can go in]. One is to try to decrease the AEs associated with transplant. This [Orca-T cell therapy] is very effective [in doing this] by targeting the graft-vs-leukemia effect and preventing GVHD. The second direction is to use these allogeneic cells to specifically target the tumor cells. That is why gene modifications, CAR T-cell therapies, and other approaches are coming. They still use allogeneic cells from a donor, but now they are directing them to specifically go after tumor cells.

Go here to read the rest:
Orca-T Offers an Alternative to HSCT With Improved Patient Experience - OncLive

Large granular lymphocytic (LGL) leukemia is a kind of cancer that affects blood cells. The disease is rare: Only about 1,000 people per year are diagnosed with it. It affects men and women in roughly equal numbers, and most of those diagnosed are over 60 years old.

Heres what we know about this form of leukemia.

Your blood is made up of four different parts:

Some of your white blood cells are larger than the rest. These cells contain tiny granules that can be seen under a microscope.

In people with LGL leukemia, these large, granular white blood cells copy themselves until there are too many. The fact that the white blood cells (also called lymphocytes) replicate themselves is what makes this disorder a type of cancer.

Your blood contains two different types of lymphocytes: T-cells (T-LGL) and B-cells, which are also known as natural killer cells (NK-LGL). B-cells fight off invading bacteria and viruses. T-cells attack other cells in your body that have become harmful, like cancer cells.

When your T-cells are copying themselves too much, you have T-LGL leukemia. If your natural killer cells are replicating too much, you have NK-LGL leukemia.

Most cases of LGL leukemia are chronic and slow-growing, whether theyre NK-LGL or T-LGL. Only around 10 percent of all LGL cases are aggressive, fast-growing cells.

Researchers dont yet know what causes LGL leukemia. The disorder is associated with a genetic change or mutation, usually to the STAT3 and STAT5b genes.

Between 10 and 40 percent of people with LGL leukemia also have a history of autoimmune disorders. The immune disorder most often associated with LGL leukemia is rheumatoid arthritis (RA).

About 20 percent of those with LGL leukemia also have RA. So far, researchers have been unable to determine which disorder began first.

Most people who are diagnosed with LGL leukemia will experience some of these symptoms:

A healthcare professional may look for other symptoms, too, including:

You should contact your doctor and seek treatment if youre having recurring infections, especially if you have a fever that doesnt go away or you have other infection symptoms, such as swelling or sores, that arent getting better.

To find out if you have LGL leukemia, a healthcare professional will analyze a sample of your blood. Your doctor may also take a sample of your bone marrow, often from your hip area, to look for abnormal cells.

To determine which type of LGL leukemia you have, your doctor could use a laser technology called flow cytometry to identify whether T-cells or NK-cells are replicating too much.

Most cases of LGL leukemia are slow growing. Doctors sometimes take a wait-and-watch approach to treatment.

You may not start treatment until tests or symptoms show that the condition has reached a certain level.

If tests show that your neutrophil levels have dropped too much, your doctor may start treatment at that time. Around 45 percent of people with this condition needed immediate treatment.

When treatment for LGL leukemia begins, it may or may not follow the same intensive course as other cancer treatments.

Most people will eventually need some combination of chemotherapy and immune-suppressing drug therapy. Your medications could include:

In some cases, treatment for LGL leukemia involves a bone marrow or stem cell transplant. Its also possible that your treatment could include removing your spleen, an organ in your abdomen that filters your blood and helps maintain your immune system.

Two to three times a year, you may need to visit a healthcare professional to have bloodwork done to monitor your health and the activity of your white blood cells.

While theres no cure for LGL leukemia, most cases progress very slowly, unlike other forms of leukemia. One study that followed 1,150 people with the disease found that they lived an average of 9 years after their diagnosis.

The more aggressive form of LGL leukemia doesnt respond well to treatment. Life expectancy is likely much shorter for those with this very rare subtype of LGL leukemia.

LGL leukemia is a rare type of cancer where large white blood cells copy themselves too much, making your body prone to frequent infections.

Most cases of LGL leukemia are slow-growing, so treatment might not be necessary at first.

Eventually, people with this condition might need a combination of chemotherapy and immunosuppressing medications to slow the growth of cancer cells. Theres no cure yet for LGL leukemia.

A small percentage of cases are a faster-growing type of leukemia that doesnt respond well to treatments. Life expectancy for this subtype is shorter than the slow-growing type.

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LGL Leukemia: Overview, Symptoms, and Treatment - Healthline

One of the common research approaches to treating brain diseases such as Parkinsons disease (PD) and Alzheimers disease (AD) is using antibodies designed to clear the accumulated misfolded proteins implicated in the diseases. To date, these drug trials have not been particularly successful at improving the disease, even when they are effective at removing the proteins. A new theory hypothesizes that the antibodies are actually increasing the neuroinflammation associated with PD and AD, basically making the disease worse while removing the proteins.

Stuart Lipton, a researcher at Scripps Research Institute, recently published research suggesting that this may be exactly what is happening. They ran a series of in vitro assays and experiments in mice that had brain grafts of human-induced pluripotent stem cell (hiPSC)-derived microglia (hiMG). They found that the antibodies that target the misfolded proteins found in PD and AD trigger the NLRP3 inflammasome, which can lead to cell death.

Our findings provide a possible explanation for why antibody treatments have not yet succeeded against neurodegenerative diseases, said co-senior author Lipton, Step Family Foundation endowed chair in the department of molecular medicine and founding co-director of the Neurodegeneration New Medicines Center at Scripps Research.

The results were published in Proceedings of the National Academy of Sciences (PNAS).

The research started when Dorit Trudler, a postdoctorate researcher in Liptons lab, attempted to make microglia in the lab. Microglia are the innate immune cells in the brain, and it is a notoriously difficult task because the cells dont originate from the same type of stem cells in the bone marrow that generates the rest of the immune system.

Instead of coming from the bone marrow like B and T cells and macrophages, microglia are created from the yolk sac that embryos swim in during early development, then migrate from the sac to the brain. Trudler was able to turn human-derived stem cells to turn into a yolk sac-like structure, and from there, developed cells that were identical to microglia removed from humans based on the mRNA they expressed.

Lipton indicated, They match as closely as possible.

They then exposed these microglia to either alpha-synuclein, the misfolded protein identified in Parkinsons patients, and the microglia shot off inflammatory signals. And when they exposed the microglia to amyloid-beta, the hallmark of Alzheimers, the inflammation grew worse.

They then worked with biopharma companies to obtain antibodies that bind to either alpha-synuclein or amyloid-beta. Although Lipton is not saying which companies, it did say one of them was not Biogens aducanumab, which is up for approval or rejection for Alzheimers by June 7 by the U.S. Food and Drug Administration (FDA).

The surprising and potentially extremely important result was that although the antibodies successfully attached to their protein targets, it didnt help with inflammation. Rather than make things better, it actually made things worse, Lipton said.

And they further found in humanized mice with both human and mice microglia, that the pro-inflammatory response was unique to the human cells. This means that biopharma companies, in working with laboratory animals on therapeutic antibodies for these diseases, would not have seen this reaction. Although unclear yet why its causing inflammation, they are convinced the NLRP3 pathway is involved, although they dont have the exact mechanism worked out. Potentially, however, it might be possible to treat patients with a combination of the protein-clearing drugs and anti-inflammatories that block the NLRP3 pathway.

In an unrelated study, researchers at Massachusetts General Hospital utilized whole-genome sequencing (WGS) to identify rare genomic variants associated with AD. In doing so, they found 13 mutations, which establish new genetic links between AD and synaptic function. They believe it could help guide the development of new drugs for AD.

The first group of genes identified that were associated with AD involve the accumulation of amyloid-beta. The next 30 AD gene mutations identified were linked to chronic inflammation in the brain. Loss of synapses is the neurological change most closely linked with the severity of dementia in AD, but until now clear genetic association had not been identified.

Rudolph Tanzi, vice chair of Neurology and director of the hospitals Genetics and Aging Research Unit, said, It was always kind of surprising that whole-genome screens had not identified Alzheimers genes that are directly involved with synapses and neuroplasticity.

Tanzi went on to note that identifying less-common mutations that increase the risk for AD may provide critical information about the disease. Rare gene variants are the dark matter of the human genome, he said.

There are many of them, as it turns out. Of the three billion pairs of nucleotide bases in the human genome, about 5o to 60 million are gene variants and 77% are rare.

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Do Therapies for Alzheimer's & Parkinson's that Clear Abnormal Brain Proteins Make the Diseases Worse? - BioSpace

MELVILLE, N.Y., March 31, 2021 (GLOBE NEWSWIRE) -- BioRestorative Therapies, Inc. (the Company) (OTC: BRTX), a life sciences company focused on stem cell-based therapies, today announced that the United States Patent Office has issued a notice of allowance for a patent application related to the Companys metabolic ThermoStem Program. The notice of allowance was issued on March 22, 2021 and is related to a new patent application not previously announced.

Claims granted under the new patent cover methodologies related to generating exosomes and brown adipocytes from human brown adipose-derived stem cells. Exosomes are small extracellular vesicles produced by cells that contain lipids, messenger-RNA, micro-RNA, cytokines and proteins. Therapeutic benefits of using exosomes have been demonstrated in various disease models and may provide a valuable therapeutic tool for treating disease.

We are pleased to see that we have been granted an additional patent by the USPTO for our ThermoStem Program, said Lance Alstodt, the Companys CEO. Our comprehensive portfolio of patents under our ThermoStem Program continues to expand as we develop and protect intellectual property related to large and growing markets where brown adipocyte therapeutics can be applied. Im very proud of our team, driving towards the achievement of our stated goals. The advancement of our technology is a core, fundamental value driver of our Company. Our family of intellectual property coupled with our financial reporting progress are critical factors contributing to our growth strategy.

It is expected that the exosome diagnostic and therapeutic market will reach $368 million by 2022 as the development of research, clinical tools and therapeutics continues to grow in this emerging technology.

About BioRestorative Therapies, Inc.

BioRestorative Therapies, Inc. (www.biorestorative.com) develops therapeutic products using cell and tissue protocols, primarily involving adult stem cells. Our two core programs, as described below, relate to the treatment of disc/spine disease and metabolic disorders:

Disc/Spine Program (brtxDISC): Our lead cell therapy candidate, BRTX-100, is a product formulated from autologous (or a persons own) cultured mesenchymal stem cells collected from the patients bone marrow. We intend that the product will be used for the non-surgical treatment of painful lumbosacral disc disorders or as a complementary therapeutic to a surgical procedure. The BRTX-100 production process utilizes proprietary technology and involves collecting a patients bone marrow, isolating and culturing stem cells from the bone marrow and cryopreserving the cells. In an outpatient procedure, BRTX-100 is to be injected by a physician into the patients damaged disc. The treatment is intended for patients whose pain has not been alleviated by non-invasive procedures and who potentially face the prospect of surgery. We have received authorization from the Food and Drug Administration to commence a Phase 2 clinical trial using BRTX-100 to treat chronic lower back pain arising from degenerative disc disease.

Metabolic Program (ThermoStem): We are developing a cell-based therapy candidate to target obesity and metabolic disorders using brown adipose (fat) derived stem cells to generate brown adipose tissue (BAT). BAT is intended to mimic naturally occurring brown adipose depots that regulate metabolic homeostasis in humans. Initial preclinical research indicates that increased amounts of brown fat in animals may be responsible for additional caloric burning as well as reduced glucose and lipid levels. Researchers have found that people with higher levels of brown fat may have a reduced risk for obesity and diabetes.

Forward-Looking Statements

This press release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. You are cautioned that such statements are subject to a multitude of risks and uncertainties that could cause future circumstances, events or results to differ materially from those projected in the forward-looking statements as a result of various factors and other risks, including, without limitation, those set forth in the Company's latest Form 10-K filed with the Securities and Exchange Commission. You should consider these factors in evaluating the forward-looking statements included herein, and not place undue reliance on such statements. The forward-looking statements in this release are made as of the date hereof and the Company undertakes no obligation to update such statements.

CONTACT:Email: ir@biorestorative.com

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BioRestorative Therapies Announces Notice of Allowance for a New Patent Application Related to its Off-the-Shelf ThermoStem Program - GlobeNewswire