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The final frontier? Studying stem cells on the International Space Station – Scope

By Stem Cell Medicine

It's not often I get to write about astronauts and space travel. In fact, it's happened exactly... never. But now, thanks to a high-flying collaboration of Stanford researchers past and present, I get to write about something that's really out of this world.

Since 2006, iPS cells (short for induced pluripotent stem cells) have been at the forefront of groundbreaking research in biology and medicine. The cells' ability to become nearly any tissue in the body makes them an invaluable resource for physicians wishing to study the effect of drugs on specific, hard-to-obtain tissues or for researchers wanting to delve into the molecular missteps that lead to all manner of diseases.

Now iPS-derived human heart muscle cells called cardiomyocytes have found their way into space, as part of a study by cardiologist and stem cell researcher Joseph Wu, MD, PhD, graduate student Alexa Wnorowski and former Stanford graduate student Arun Sharma, PhD. With the help of NASA astronaut Kate Rubins, PhD, (also a former Stanford graduate student!), Wnorowski and Sharma studied the effect of the low gravity of the International Space Station on the heart cells' structure and function.

They published their findings today in Stem Cell Reports.

As Sharma, now a senior research fellow at Cedars-Sinai, explained in an email:

This project represented an opportunity for biomedical researchers to collaborate with astronauts and engineers in order to learn more about how a very unique environment, microgravity, affects the cells of the human heart.

Sharma, Wnorowski and Wu found that the cardiomyocytes cultured on the space station exhibited different patterns of gene expression than did their counterparts grown back here on Earth. They also displayed changes in the way they handled calcium -- an important regulator of contraction rate and strength.

Interestingly (and perhaps reassuringly for astronauts like Rubins), the cells appeared to return to normal when their five-and-a-half week jaunt into low Earth orbit ended.

"Working with the cells that launched to and returned from the International Space Station was an incredible opportunity," Wnorowski said. "Our study was the first conducted on the station that used human iPS technology, and demonstrated that it is possible to conduct long-term, human cell-based experiments in space."

All in all, the researchers were interested to see how nimbly the cells adjusted to their new, free floating life.

"We were surprised by how quickly human heart cells adapted to microgravity," Sharma said. "These results parallel known organ-level adaptations that happen to the heart during spaceflight."

Photos of Kate Rubins by NASA

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The final frontier? Studying stem cells on the International Space Station - Scope

Super-grafts That Could Treat Diabetes – Technology Networks

By Stem Cell Medicine

To save patients with a severe form of type 1 diabetes (characterized by the absence of functional insulin-producing cells), pancreatic cell transplantation is sometimes the last resort. The pancreas contains cell clusters called islets of Langerhans where cells that produce blood glucose regulating hormones are grouped together. However, the transplant process is long and complex: a significant part of the grafted cells die quickly without being able to engraft. By adding amniotic epithelial cells to these cell clusters, researchers at the University of Geneva (UNIGE) and the Geneva University Hospitals (HUG), Switzerland, have succeeded in creating much more robust super-islets of Langerhans. Once transplanted, more of them engraft; they then start producing insulin much more rapidly. These results, to be discovered in Nature Communications, would not only improve the success of cell transplants, but also offer new perspectives for other types of transplants, including stem cell transplantation.

Today, islet transplantation is one of the last-chance options for patients with a particularly severe form of type 1 diabetes. The islets are removed from a donors pancreas, isolated and then re-injected into the patients liver. The procedure is well controlled about fifteen patients benefit from it every year in Switzerland but nevertheless complex, says Ekaterine Berishvili, a researcher in the Department of Surgery at UNIGE Faculty of Medicine, who led this work. Many of the islets die along the way. It often takes several donors to treat one person, whereas we are in desperate need of donors.

Placental cells to help grafts

To improve the success of islet transplantation and the survival of transplanted cells, researchers in Geneva have sought to create new, more robust islets that would withstand the stress of transplantation better than natural islets. To do this, they came up with the idea of adding amniotic epithelial cells, taken from the wall of the inner placenta membrane, to the pancreatic cells. These cells, very similar to stem cells, are already used in other therapies, such as corneal repair for example, says Thierry Berney, Professor in the Department of Surgery at UNIGE Faculty of Medicine and Head of HUG Transplant Division, who co-directed this work. In our case, we found that they can promote the function of pancreatic cells, which is to produce hormones according to fluctuations in sugar levels.

First step, in vitro: the addition of amniotic epithelial cells allowed the cell clusters to form regular spheres, indicating better intracellular communication and connectivity. Second step in vivo: the scientists transplanted their super-islets of Langerhans into diabetic mice, which quickly began to produce insulin. Even with few cell clusters, our super islets adapted very well to their new environment and quickly became vascularized, says Fanny Lebreton, a researcher in the Department of Surgery at UNIGE Faculty of Medicine and the first author of this work. A good vascularization is indeed the key element of any transplantation: it allows to supply the new organ with oxygen and nutrients and guarantees their survival. In addition, the artificial islets quickly began to produce insulin.

Improving oxygenation and protecting islets

Amniotic epithelial cells are thus essential to islet survival and seem to act on two vital elements: the lack of oxygen, which usually kills a large number of transplanted islets, and the modulation of the host immune system to limit the risk of rejection. In any transplant, the first step is to lower the recipients immunity to limit the risk of rejection, says Ekaterine Berishvili. Amniotic epithelial cells have the unique characteristic of protecting the foetus, which is also a non-self, from attacks by its mothers immune system. We believe that the same mechanism is at work to protect the grafts. The protective mechanism, observed here on cell transplants, could also take place in other types of transplants or even in xenotransplantation where non-human cells or organs are transplanted into humans.

These discoveries now need to be confirmed on human subjects. Since the use of amniotic epithelial cells is already common in other clinical settings without adverse side effects, this could be done relatively quickly. An important hope for all those awaiting a transplant.

Reference:Lebreton, F., Lavallard, V., Bellofatto, K., Bonnet, R., Wassmer, C. H., Perez, L., Berishvili, E. (2019). Insulin-producing organoids engineered from islet and amniotic epithelial cells to treat diabetes. Nature Communications, 10(1). https://doi.org/10.1038/s41467-019-12472-3

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Space travel affects heart cells, but only temporarily – BBC Focus Magazine

By Stem Cell Medicine

The thought of spaceflight may make the heart skip a beat, but actually travelling beyond Earth could alter the organs cells.

With extended stays aboard the International Space Station (ISS) commonplace, and the likelihood of humans spending longer periods in space increasing, there is a need to better understand the effects of micro-gravity on cardiac function.

New research suggests heart muscle cells derived from stem cells have a remarkable ability to adapt to their environment during and after spaceflight.

Scientists examined cell-level cardiac function and gene expression in human heart cells cultured aboard the International Space Station for five-and-a-half weeks.They found that exposure to micro-gravity changed the expression of thousands of genes, but largely normal patterns reappeared within 10 days after returning to Earth.

Read more about the body in space:

Senior study author, Joseph Wu, of Stanford University School of Medicine, said: Our study is novel because it is the first to use human induced pluripotent stem cells to study the effects of spaceflight on human heart function.

Micro-gravity is an environment that is not very well understood, in terms of its overall effect on the human body, and studies like this could help shed light on how the cells of the body behave in space, especially as the world embarks on more and longer space missions such as going to the Moon and Mars.

Until now, most studies on how the heart reacts to micro-gravity have been conducted in either non-human models or at tissue, organ or systemic level.To address this, the beating cells were launched to the ISS aboard a SpaceX spacecraft as part of a commercial resupply service mission.Simultaneously, they were also cultured on Earth for comparison purposes.

When they returned to the planet, the cells showed normal structure and morphology.However, they did adapt by modifying their beating pattern and calcium recycling patterns.

Immunofluorescence imaging of the cells grown in micro-gravity aboard the International Space Station Joseph Wu lab, Stanford University School of Medicine/PA

Researchers sequenced the cells harvested at four-and-a-half weeks aboard the ISS, and 10 days after returning to Earth.Results showed that 2,635 genes were differentially expressed among flight, post-flight, and ground control samples.

Most notably, gene pathways related to mitochondrial function were expressed more in the space-flown cells, according to the research published in the Stem Cells Reports journal.

A comparison of the samples revealed the space cells adopted a unique gene expression pattern during spaceflight, which reverted to one that is similar to ground-side controls upon return to normal gravity.

Dr Wu added: Were surprised about how quickly human heart muscle cells are able to adapt to the environment in which they are placed, including micro-gravity.

These studies may provide insight into cellular mechanisms that could benefit astronaut health during long-duration spaceflight, or potentially lay the foundation for new insights into improving heart health on Earth.

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Oct4, Considered Vital for Creating iPSCs, Actually Isnt Needed – The Scientist

By Embryonic Stem Cells

Since 2006, when Shinya Yamanaka, now the director of the Center for iPS Cell Research and Application at Kyoto University, discovered a method that could guide fully differentiated cells back to their pluripotent state, scientist have been using his recipe to produce induced pluripotent stem cells. The protocol relies on overexpressing the so-called Yamanaka factors, which are four transcription factors: Oct4, Sox2, Klf4, and cMyc (OSKM). While the technique reliably creates iPS cells, it can cause unintended effects, some of which can lead to cells to become cancerous. So researchers have worked to adjust the cocktail and understand the function of each factor.

No one had succeeded in creating iPS cells without forcing the overexpression of Oct4. It was thought that this was the most crucial factor of the four. At least until now.

If this works in adult human cells, it will be a huge advantage for the clinical applications of iPS cells.

Shinya Yamanaka, Kyoto University

Four years ago, Sergiy Velychko, a graduate student at the Max Planck Institute for Molecular Biomedicine in Hans Schlers lab, and his team were studying the role of Oct4 in creating iPS cells from mouse embryonic fibroblasts. He used vectors to introduce various mutations of the gene coding for Oct4 to the cells he was studying, along with a negative controlone that didnt deliver any Oct4. He was shocked to discover that even using his negative control, he was able to generate iPS cells.

Velychkos experiment was suggesting that it is possible to develop iPS cells with only SKM.

We just wanted to publish this observation, Velychko tells The Scientist, but he knew hed need to replicate it first because reviewers wouldnt believe it.

He and his colleagues, including Guangming Wu, a senior scientist in the lab, repeated the experiment several times, engineering vectors with different combinations of the four factors. SKMthe combination that didnt include Oct4was able to induce pluripotency in the cells with about 30 percent of the efficiency of OSKM, but the cells were of higher quality, meaning that the researchers didnt see evidence of common off-target epigenetic effects. They reported their results yesterday (November 7) in Cell Stem Cell.

Efficiency is not important. Efficiency means how many colonies do you get, explains Yossi Buganim, a stem cell researcher at the Hebrew University of Jerusalem, who was not involved in the study. If the colony is of low quality, the chances that eventually the differentiated cells will become cancerous is very high.

Finally, the team employed the ultimate test, the tetraploid complementation assay, in which iPS cells are aggregated with early embryos that otherwise would not have been able to form a fully functional embryo on their own. These embryos grew into mouse pups, meaning that the iPS cells the team created were capable of maturing into every type of cell in the animal.

Whats more is they found that the SKM iPS cells could develop into normal mouse pups 20 times more often than the OSKM iPS cells, suggesting that the pluripotency of iPS cells can be greatly improved by omitting Oct4 from the reprogramming factor cocktail.

The results will need to be verified in human cells, Buganim cautions. His team has developed methods for creating iPSCs that worked well in mouse cells only to be completely ineffective in humans.

Yamanaka himself was enthusiastic about the results, telling The Scientist in an email that his team would definitely try the method in other cell types, especially adult human blood cells and skin fibroblasts. If this works in adult human cells, it will be a huge advantage for the clinical applications of iPS cells.

S.Velychkoet al.,Excluding Oct4 from Yamanaka cocktail unleashes the developmental potential of iPSCs,Cell Stem Cell,doi:10.1016/j.stem.2019.10.002,2019.

Emma Yasinski is a Florida-based freelance reporter. Follow her on Twitter@EmmaYas24.

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Oct4, Considered Vital for Creating iPSCs, Actually Isnt Needed - The Scientist

Impact Of ELN Risk Stratification, Induction Chemotherapy Regimens And | CMAR – Dove Medical Press

By Stem Cell Medical Center

Shanglong Feng,1,* Li Zhou,2,* Xinhui Zhang,1,* Baolin Tang,2 Xiaoyu Zhu,2 Huilan Liu,2 Zimin Sun,2 Changcheng Zheng1,2

1Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, Peoples Republic of China; 2Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Peoples Republic of China

*These authors contributed equally to this work

Correspondence: Changcheng ZhengDepartment of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei 230001, Peoples Republic of ChinaTel/fax +86-551-62284476Email zhengchch1123@ustc.edu.cn

Background: Hyperleukocytic acute myeloid leukemia (AML) (initial white blood cell count100 109/L) is a clinical emergency often accompanied by leukostasis syndrome, tumor lysis syndrome (TLS), and disseminated intravascular coagulation (DIC), with a poor clinical prognosis. The aim of this study retrospectively analyzed the clinical features of hyperleukocytic AML, focusing on high-risk factors affecting prognosis, the selection of initial induction therapy, and the impact of hematopoietic stem cell transplantation (HSCT) on prognosis.Patients and methods: A total of 558 AML patients at our center from January 2013 to December 2017 were diagnosed, and 52 (9.32%) patients presented with hyperleukocytosis were retrospectively reviewed.Results: The 3-year overall survival (OS) rate in the 1539 years old and 4060 years old group was 58.8% and 25.4%, respectively; the longest survival time in patients aged >60 years was only 8 months, and the 8-month OS rate was 8.3% (p=0.002). The 3-year OS rate of the patients in the favorable risk group, intermediate risk group and high risk group, according to the 2017 ELN risk stratification, was 50%, 28.0%, and 29.5%, respectively (p=0.374). The 3-year OS rate of patients carrying CEBPA or NPM1 mutation and those with FLT3-ITD or MLL mutation was 37.5% and 30.0%, respectively (p=0.63). The 3-year OS rate of patients employing an induction regimen of a standard IA regimen was 58.4%, and of those employing a non-standard IA regimen was 22.2% (p=0.065). The 3-year OS rate of the transplantation patients reached 73.8%, while the 9-month OS rate of patients without transplantation was 11.4% (p<0.001).Conclusion: This study suggest that hyperleukocytosis is an independent risk factor for AML patients, regardless of the risk stratification based on cytogenetic or molecular abnormalities. Age is the main factor influencing the prognosis of hyperleukocytic AML. The use of a standard IA regimen and HSCT can significantly improve the patients prognosis.

Keywords: acute myeloid leukemia, hyperleukocytosis, ELN risk stratification, induction chemotherapy, hematopoietic stem cell transplantation

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Impact Of ELN Risk Stratification, Induction Chemotherapy Regimens And | CMAR - Dove Medical Press

An artist and a transplant researcher discuss the heart – Harvard Gazette

By Stem Cell Medical Center

Doris A. Taylors so-called replacement ghost heart suggests something otherworldly, but the eerie-looking form is far from an apparition. Its an innovative approach to organ transplantation that has inspired many in the medical community and at least one artist.

The Texas researchers process piggybacks on natures sophisticated design. Together she and a team of researchers strip cells off human and animal cadaver hearts with a soapy solution, leaving ghostly white protein shells that retain the form of the organ. They inject them with a patients blood or bone-marrow stem cells, and the ghost hearts act as scaffolding on which the newly introduced cells can slowly transform into a beating muscle.

What we said was, Wouldnt it be really cool if we could wash the sick cells out and put the healthy cells back in? said Taylor, director of Regenerative Medicine Research and director of the Center for Cell and Organ Biotechnology at the Texas Heart Institute, during a recent talk at the Radcliffe Institute for Advanced Study.

The hope is that one day these regenerated hearts will resolve the most challenging issues transplant patients currently face: the lack of a permanent artificial replacement, concerns about rejection, and the shortage of viable donor hearts.

Taylors efforts are driving what could become a revolution in organ transplants, and they have sparked the creativity of transdisciplinary artist Dario Robleto, whose latest work, on view at the Johnson-Kulukundis Family Gallery in Radcliffes Byerly Hall, recreates in images and sounds the original pulse wave of the heart first captured in visual form by scientists in the 1900s. Robleto and Taylor, longtime friends and Texas residents, explored those connections during Mondays Radcliffe discussion, which was moderated by Jennifer Roberts, Elizabeth Cary Agassiz Professor of the Humanities.

Robletos exhibit, Unknown and Solitary Seas, touches on the overlap between the medical mysteries and workings of the vascular pump, and the metaphor for the heart as the emotional center of the soul. It includes a video installation that features recreated sounds of a beating heart from the 19th century, reconstructed images of how the earliest pulse waves first appeared on the page, and a series of heart waveform sculptures in brass-plated stainless steel.

Roberts said that with his work, Robleto acknowledges the pulse waves promise, their profundity, their scientific value, but he also reclaims some of their ambiguity and asks us to wonder whether we can or should accept that these waveforms have escaped the realms of art, culture, and emotional communication.

Taylor similarly views her work as a blend of the scientific and the human. It transcends complicated, complex science, she says, in that her ghost hearts require a kind of passion, commitment, care, attention, and nurturing similar to whats required by a small child. Its really about building hearts at the emotional, mental, spiritual, and physical level that I think is going to get them to work, she said.

For Robleto, big ideas, like the creation of a new human heart, require multiple perspectives.

The artist called Taylors work one of the most fascinating and definitely one of the most emotional things Ive ever seen. As an object, he added, the ghost heart is stunningly beautiful but it also raises questions about the self, identity, emotion, the notions of form and where memory is truly held, questions he thinks artists can help address. He cited two of the nations earliest heart transplants, after which the patients wives asked their husbands, who had received donor hearts, if they still loved them.

Taylors work, Robleto said, is right at the edge of identity and materiality and so when the day comes when someone says the first ghost heart transplant I think we will have a similar moment where perhaps we will be forced to re-evaluate what we ask from our heart metaphor.

Dario Robletos Unknown and Solitary Seas is on view in Byerly Halls Johnson-Kulukundis Family Gallery through Jan. 18, 2020.

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Novel Molecule Reduces the Aggressiveness of Pediatric Cancer – Technology Networks

By Stell Cell Research

In Brazil, scientists affiliated with the Human Genome and Stem Cell Research Center (HUG-CELL) at the University of So Paulo (USP) have identified a molecule capable of reducing the aggressiveness of embryonal central nervous system tumors. These are malignant tumors that start in fetal cells in the brain and mainly affect children up to four years old.

The results arepublishedin the journalMolecular Oncology.HUG-CELLis one of the Research, Innovation and Dissemination Centers (RIDCs) supported by So Paulo Research Foundation - FAPESP. Its principal investigator isMayana Zatz, Professor of Human and Medical Genetics at USP's Institute of Biosciences (IB).

The approach proposed by the group can be classified as a type of microRNA-based therapy. A microRNA is a small RNA molecule that does not encode protein but plays a regulatory role in the genome. In this study, researchers used a synthetic version of an inhibitor of microRNA-367 (miR-367) with anti-tumor activity.

"We demonstrated in an animal model of a central nervous system tumor that treatment with a microRNA inhibitor attenuates properties of tumor stem cells and prolongs survival," saidOswaldo Keith Okamoto, a professor at IB-USP and the principal investigator for the study.

Okamoto explained that embryonal central nervous system tumors such as medulloblastomas and atypical teratoid/rhabdoid tumors (AT/RTs) tend to contain cells with characteristics similar to those of stem cells, which boosts their tumorigenic potential and capacity to invade tissue while also making them more resistant to cell death.

These tumors are caused by genetic or epigenetic aberrations in stem cells and neural progenitors when the nervous system is being formed during embryonic development. The neural stem cells that undergo these alterations later give rise to tumor cells. They form aggressive, fast-growing tumors that may appear shortly after birth, in later childhood or in adolescence.

In a previous study, the group tested an approach that used the Zika virus to destroy tumor stem cells (read more atagencia.fapesp.br/27677).

Expression and inhibition

A more recent study was led byCarolini Kaid, a postdoctoral researcher at IB-USP with a scholarship fromFAPESP.

Previous research has already shown that OCT4A, one of the genes that encode pluripotency factors, is overexpressed in aggressive medulloblastomas and that this overexpression is associated with an unfavorable prognosis. During hermaster's research, Kaid detected the expression of miR-367, a gene that promotes stem-like traits in tumor cells, in parallel with overexpression of OCT4A (read more atagencia.fapesp.br/21959).

The researchers then tested a specific synthetic inhibitor of miR-367 containing minor chemical alterations that make it more stable in cells. A patent application has been filed for the invention.

After inducing the formation of central nervous system tumors in mice using three different strains of tumor cells, the researchers injected the miR-367 inhibitor into the brain's right lateral ventricle, a pathway to the cerebrospinal fluid that surrounds the brain and spinal cord. From there, the miR-367 inhibitor was able to access the tumor cells.

Tumor size was reduced considerably, and survival improved in all groups of mice. The results confirmed what had previously been observed in cell cultures.

In this model, the researchers noted that when the synthetic molecule interacted with miR-367 in tumor cells, it prevented this microRNA from affecting the levels of proteins it normally regulates, such as ITGAV and SUZ12.

The latter is known to be involved in silencing pluripotency-related genes in embryonic stem cells.

While the role of ITGAV in embryonal central nervous system tumors is not fully understood, ITGAV is known to participate in the renewal of both normal and tumor stem cells.

"When miR-367 is inhibited in cancer cells, it stops regulating several proteins. This molecular alteration eventually affects the properties of these cells, resulting in an attenuation of the tumor's aggressiveness. This is what makes the strategy interesting," Kaid said.

The researchers believe that in humans, the synthetic molecule alone may be capable of at least containing the development of these tumors and improving survival. Even so, they are testing combinations of the molecule with drugs currently used to treat the tumors. They want to find out whether the approaches could be combined using lower doses of chemotherapy drugs.

Before clinical trials can be performed, however, pharmacology and toxicity studies will be necessary, as will pharmacokinetic testing to show how the molecule is metabolized and how long it stays in the organism (its half-life).

When embryonal central nervous system tumors are conventionally treated with surgery, chemotherapy and/or radiotherapy, morbidity and mortality rates for these patients are high. These tumors correspond to 10% of all central nervous system cancer cases in children.

Even patients who survive longer than most may suffer from permanent treatment-related sequelae that impair their quality of life, such as problems with development, cognition, locomotion and speech.

Reference: Kaid et al. 2019.miR367 as a therapeutic target in stemlike cells from embryonal central nervous system tumors. Molecular Oncology. DOI: https://doi.org/10.1002/1878-0261.12562.

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2019s Allen Distinguished Investigators will focus on the mysteries of our cells – Yahoo Tech

By Stell Cell Research

The Paul G. Allen Frontiers Group, a division of Seattles Allen Institute, is making a total of $7.5 million in awards to its latest class of five biomedical researchers.

The themes for this years Allen Distinguished Investigators focus on stem cell therapies and single-cell interactions in their native environments.

The field of stem cell biology has the potential to change how we treat diseases by helping precision medicine, and theres so much we still dont understand about the interplay between cells in living tissues or organs, Kathy Richmond, director of the Frontiers Group, said today in a news release.

Our 2019 Allen Distinguished Investigators are pushing their fields in these two areas, through new technology development, probing pivotal interactions in the body that cause health to fail, and generating creative new stem cell models that will improve our understanding of different human diseases, she said.

The late Microsoft co-founder Paul Allen gave the Allen Distinguished Investigator program its start in 2010 as a way to support significant early-stage research thats less likely to receive grants from traditional sources. This years selections bring the roster to a total of 74 researchers, including 13 from the University of Washington.

Each of the investigators will receive $1.5 million in support for their projects over three years. Heres a rundown on the Class of 2019:

The 2019 Allen Distinguished Investigators include Samantha Morris of Washington University in St. Louis, Joshua Rabinowitz of Princeton University, Clive Svendsen of Cedars-Sinai Medical Center, Savas Tay of the University of Chicago and James Wells of Cincinnati Childrens Hospital Medical Center. (Allen Institute Photos)

Samantha Morris of Washington University in St. Louis aims to create a blueprint of cell identity that will enable researchers to improve the way they generate different kinds of cells from human stem cells.

Joshua Rabinowitz of Princeton University will lead a team developing new technologies to study metabolites, the molecules that result from our bodies conversion of food into energy, as well as metabolic activity in single cells from mouse and human tissue.

Clive Svendsen of Cedars-Sinai Medical Center will use stem cells to model how interactions between the gut microbiome and the brain might influence neuron death in patients with Parkinsons disease.

Savas Tay and his colleagues at the University of Chicago are looking into the roots of Crohns disease by combining the study of gene expression with single-cell measurements of proteins and protein complexes, using samples of healthy and diseased gut tissue.

James Wells and his colleagues of Cincinnati Childrens Hospital Medical Center will use stem cells to study maladies that affect enteroendocrine cells, which sense nutrients from the food we eat and then control how those nutrients are processed in the intestines.

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2019s Allen Distinguished Investigators will focus on the mysteries of our cells - Yahoo Tech

At the American Academy of Stem Cell Physicians Live Congress 2019, FDA Safety Panel Says No to the Bad Actors – PRNewswire

By Stell Cell Research

MIAMI, Nov. 7, 2019 /PRNewswire/ -- The American Academy of Stem Cell Physicians (AASCP) was joined by the alliance leader Janet Marchibroda in hosting a safety standards panel on Nov. 2 at the AASCP Live Congress 2019. The panel which was moderated by Janet Marchibroda, the president of The Alliance for cell therapy now, and included attendance via Skypeby Dr. Peter Marks, director of the Center for Biologics and Evaluation and Research was well-received by physicians from around the world.

The panel discussed safety precautions and considered guidelines for the safety of patients, calling out the bad actors in the field. They noted that current safety guidelines are antiquated and need revision to meet the demands of new cutting-edge medicine such as stem cells, which is a growing field in medical biologics.

Dr. A.J. Farshchian, a spokesperson forthe AASCP, was honored with the 2019 Visionary Award for his pioneering work with the AASCP and the stem cell industry. He said, "There's been too much talk but no action. We need to change that to ensure the safety of the patients who receive care. AASCP will gladly point out the bad actors to the FDA, are we telling on each other? Yes. Are we breaking the Code? No, we are just preserving what's left of this industry."

Later he added, "Many physicians and scientists are starting to believe that some of the regulations regarding stem cells which have been written many years ago have not kept up with the rapidly advancing science. These regulations must be revisited because they are all pass."

At the AASCP Live Congress, board certifications were also provided. To receive the board certification, physicians must meet stringent qualifications, including attending weekly meetings and pass a written and oral exam. The AASCP congratulates those who were recognized, including Dr. Rene Blaha, Dr. Warren Bleiweiss, Dr. Paula Marchionda and Dr. Kalpana Patel, all of whom received diplomat status; and Dr. Max Citrin, who received associate diplomat status.

The American Academy and its board also granted the title of associate professor and all rights therein to Dr. Richard Hull and Dr. Leonid Macheret. Dr. Richard Hull, who also earned tenure with the AASCP, said of the conference, "It is a great pleasure teaching this group of physicians. I love to teach and these physicians are so eager to learn."

To learn more about the AASCP, their educational initiatives and certification, visit AASCP.net.

About AASCP

The American Academy of Stem Cell Physicians (AASCP) is an organization created to advance research and the development of therapeutics in regenerative medicine, including diagnosis, treatment, and prevention of disease related to or occurring within the human body. The AASCP aims to serve as an educational resource for physicians, scientists, and the public. To learn more, visit AASCP.net

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MD Anderson Partners with Takeda to Develop CAR Natural Killer-Cell Therapy – Cancer Network

By Stell Cell Research

The University of Texas MD Anderson Cancer Center and Takeda Pharmaceutical Company Limited have entered an exclusive license agreement and research agreement to develop and market chimeric antigen receptor-directed natural killer (CAR NK)-cell therapies.

Under the agreement, Takeda will receive access to MD Andersons treatment platform in order to develop and commercialize the CAR NK-cell therapies for up to 4 programs, according to the announcement made Tuesday.

With their expertise in hematologic malignancies and commitment to developing next-generation cell therapies, Takeda is the ideal collaborator to help our team advance CAR NK-cell therapies to patients in need of treatments, said Katy Rezvani, MD, PhD, a professor of stem cell transplantation and cellular therapy at MD Anderson.

The therapy has a similar strategy to the much-touted CAR T-cell therapy, which shows major promise in many cancers, by collecting certain white blood cells of patients, arming them with targeted surface receptors to battle the subjects particular cancer, and then infusing them back into the patients blood.

However, chemotherapy may leave some patients without sufficient autologous T cells in their blood for treatment with CAR T-cell therapy, while others may not have the time that is required for a laboratory to generate enough T cells, according to the researchers.

CAR NK-cell therapy, developed at MD Anderson, uses natural killer cells from cord blood. The team has said that it allows production of a therapy that doesnt have to be tailored for each and every patientand also obviates the possibility of graft-versus host disease, which is a danger with some T-cell varieties.

The MD Anderson team used a retrovirus to introduce new genes into the NK cells: CD19 is added to increase the CAR NK specificity for B-cell malignancies; interleukin 15 (IL15) is added to prolong the present of the cells in the body; and a CASP9-based suicide gene as a kind of safety measure, which can be activated to trigger apoptosis by small-molecule dimerizers if there is toxicity after infusion.

In announcing the agreement, MD Anderson and Takeda emphasized that the off-the-shelf CAR NK treatment could be administered at outpatient locations.

So far, the treatment has proven safe: An ongoing phase I/2a clinical study in patients with relapsed and refractory B-cell malignancies showed that the CD19 CAR NK-therapy has not been associated with the severe cytokine release syndrome or neurotoxicity observed with existing CAR-T therapies.

Takeda said they plan to initiate a pivotal study of the CD19 CAR NK-cell therapy in 2021.

MD Anderson receives an upfront payment that was unspecified by the parties as part of the deal, as well as tiered royalties on eventual net sales, according to the statement.

Rezvani said the goal is to make therapies that get to patients and ultimately change lives.

Our vision is to improve upon existing treatments by developing armored CAR NKs that could be administered off-the-shelf in an outpatient settingenabling more patients to be treated effectively, quickly, and with minimal toxicities, said Rezvani.

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MD Anderson Partners with Takeda to Develop CAR Natural Killer-Cell Therapy - Cancer Network

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