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.

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.

Continued here:
Novel Molecule Reduces the Aggressiveness of Pediatric Cancer - Technology Networks

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.

See the original post:
Oct4, Considered Vital for Creating iPSCs, Actually Isnt Needed - The Scientist

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

See original here:
The final frontier? Studying stem cells on the International Space Station - Scope

Heart muscle cells derived from stem cells show remarkable adaptability to their environment during and after spaceflight, according to a study publishing November 7 in the journal Stem Cell Reports.

The researchers examined cell-level cardiac function and gene expression in human heart cells cultured aboard the International Space Station for 5.5 weeks. Exposure to microgravity altered the expression of thousands of genes, but largely normal patterns of gene expression reappeared within 10 days after returning to Earth.

"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," says senior study author Joseph C. Wu of Stanford University School of Medicine.

"Microgravity 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."

Past studies have shown that spaceflight induces physiological changes in cardiac function, including reduced heart rate, lowered arterial pressure, and increased cardiac output. But to date, most cardiovascular microgravity physiology studies have been conducted either in non-human models or at tissue, organ, or systemic levels. Relatively little is known about the role of microgravity in influencing human cardiac function at the cellular level.

To address this question, Wu and his collaborators (including graduate student Alexa Wnorowski, former Stanford graduate student Arun Sharma, now a research fellow at Cedars-Sinai in Los Angeles, and former Stanford graduate student turned astronaut Kathleen Rubins) studied human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). They generated hiPSC lines from three individuals by reprogramming blood cells, and then differentiated them into hiPSC-CMs.

Beating hiPSC-CMs were then launched to the International Space Station aboard a SpaceX spacecraft as part of a commercial resupply service mission. Simultaneously, ground control hiPSC-CMs were cultured on Earth for comparison purposes.

Upon return to Earth, space-flown hiPSC-CMs showed normal structure and morphology. However, they did adapt by modifying their beating pattern and calcium recycling patterns.

In addition, the researchers performed RNA sequencing of hiPSC-CMs harvested at 4.5 weeks aboard the International Space Station, and 10 days after returning to Earth. These 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 space-flown hiPSC-CMs. A comparison of the samples revealed that hiPSC-CMs adopt a unique gene expression pattern during spaceflight, which reverts to one that is similar to groundside controls upon return to normal gravity.

"We're surprised about how quickly human heart muscle cells are able to adapt to the environment in which they are placed, including microgravity," Wu says. "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."

According to Wu, limitations of the study include its short duration and the use of 2D cell culture. In future studies, the researchers plan to examine the effects of spaceflight and microgravity using more physiologically relevant hiPSC-derived 3D heart tissues with various cell types, including blood vessel cells. "We also plan to test different treatments on the human heart cells to determine if we can prevent some of the changes the heart cells undergo during spaceflight," Wu says.

Research Report: "Effects of Spaceflight on Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Structure and Function"

Related LinksCell PressSpace Medicine Technology and Systems

With the rise of Ad Blockers, and Facebook - our traditional revenue sources via quality network advertising continues to decline. And unlike so many other news sites, we don't have a paywall - with those annoying usernames and passwords.

Our news coverage takes time and effort to publish 365 days a year.

If you find our news sites informative and useful then please consider becoming a regular supporter or for now make a one off contribution.

Original post:
Human heart cells are altered by spaceflight, but return mostly to normal on Earth - Space Daily

The American Academy of Stem Cell Physicians hosted the panel on Nov. 2 to discuss safety standards for Physicians who practice stem cell medicine.

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

Related Images

dr-farshchian.jpg Dr. Farshchian

View original content to download multimedia:http://www.prnewswire.com/news-releases/at-the-american-academy-of-stem-cell-physicians-live-congress-2019-fda-safety-panel-says-no-to-the-bad-actors-300954102.html

View original post here:
At the American Academy of Stem Cell Physicians Live Congress 2019, FDA Safety Panel Says No to the Bad Actors - Yahoo Finance

KINGSTON, R.I. Nov. 4, 2019 As part of this years Religion in America Honors Colloquium, Dr. Jeremy Sugarman will visit the University of Rhode Island to share his thoughts on the inevitable tangling of religion and medicine, and the ethical issues that arise when religious and secular values collide. He will also discuss the emergence of secular bioethics, and spend time analyzing a real-world example.

The lecture, Ethical Controversies in Medicine and Medical Research: The Interplay of Secular Bioethics and Religion, will take place Tuesday, Nov. 12, at 7 p.m. in Edwards Hall, 64 Upper College Road, on the Kingston Campus. This event will not be livestreamed, nor will it be archived. It is free and open to the public.

Sugarman is an internationally recognized leader in the field of biomedical ethics, and has particular expertise in applying empirical methods and evidence-based standards to evaluate and analyze bioethical issues. He is the Harvey M. Meyerhoff Professor of Bioethics and Medicine, professor of medicine, professor of Health Policy and Management, and deputy director for medicine of the Berman Institute of Bioethics at the Johns Hopkins University.

In the past, Sugarman has researched and made contributions to medical ethics and policy, including but not limited to his work on the ethics of informed consent, umbilical cord blood banking, stem cell research, international HIV prevention research and global health and research oversight. Sugarman is the author of more than 300 articles, reviews and book chapters.

Dr. Sugarman consults and speaks internationally on a range of issues related to bioethics. He served as senior policy and research analyst for the White House Advisory Committee on Human Radiation Experiments, consultant to the National Bioethics Advisory Commission, and Senior Advisor to the Presidential Commission for the Study of Bioethical Issues. He also served on the Maryland Stem Cell Research Commission. Sugarman is a member of the Scientific and Research Advisory Board for the Canadian Blood Service and the Ethics and Public Policy Committees of the International Society for Stem Cell Research. He is co-chair of the Johns Hopkins Institutional Stem Cell Research Oversight Committee. In addition, he is chair of the Ethics Working Group of the HIV Prevention Trials Network and co-leads the Ethics and Regulatory Core of the NIH Health Care Systems Research Collaboratory.

Dr. Sugarman has been elected as a member of the American Society of Clinical Investigation, the Association of American Physicians, and the Institute of Medicine. He is a fellow of the American Association for the Advancement of Science, the American College of Physicians and the Hastings Center.

Lauren Poirier, an intern in the Marketing and Communications Department at URI and public relations and English major, wrote this press release.

Continue reading here:
Johns Hopkins professor to lecture on interplay of secular bioethics, religion as part of Honors Colloquium - URI Today