Category Archives: Cell Medicine

Until the myth of the fountain of youth proves true, regenerative medicine is the best hope weve got for fixing failed body parts and, as a result, living longer. Scientists wont be able to bottle forever. They are, however, working on engineering human cells, tissues, and organs that can repair themselves.

Basically, theyre trying to heal body parts using cells or tissue grown from stem cells, and by prompting regeneration with biologically active drugs that would essentially restart parts by forcing new growth, among other approaches. But its still a speculative venture, say Goldman Sachs analysts in an April 4 report on venture capital going into this novel frontier.

Perfecting processes for regenerating body parts is no mean feat, technically speaking. Plus, there are ethical questions to resolve and regulatory hurdles to overcome. In other words, itll take a while before new parts are available.

Nonetheless, investors are interested in the field, and especially in companies working with stem cells. Goldman analysts believe regenerative medicine is attractive because of its vast potential to eventually cure common and rare diseases in almost any tissue or organ, including the heart, liver, and lungs.

So, moneys going to regenerative medicine, at a rate of hundreds of millions of dollars annually. In 2010, the field attracted about $200 million in venture capital and in 2016, that figure had quadrupled. Stem cell technology attracts the vast majority of investment; $700 million of the $800 million dedicated to regenerative medicine in 2016 went to stem cell projects.

But analysts noted that the number of deals hasnt increased accordingly. Between 2010 and 2016 deals remained in a range of 30 to 40 while investment rose pretty steadily. This suggests that a few companies attracted larger investments per deal over time from venture capital firms.

Companies partnered with science giantslike BlueRock Therapeutics, which works with stem cell pioneer and Nobel laureate Shinya Yamanaka of Kyoto Universityget the largest investments and valuations, according to Goldman Sachs.

Analysts also remarked on Unity Biotechnology, which is developing a technique to eliminate senescent cellsor expiring cellsto increase longevity and maintain youthfulness, and has been shown to work in mice. Senescence is like a biological emergency brake cells use to stop dividing and multiplying out of control. But after the brakes been pulled, the senescent cells remain and accumulate, secreting inflammatory molecules that harm neighboring cells and tissues. Selectively removing them could keep people younger, healthier longer, according to the company.

Scientists seek funding from public sources too, of course. At the University of Washingtons Institute for Stem Cell and Regenerative Medicine, for example, researchers are manipulating stem cells to heal and restore the function in hearts, eyes, kidneys and other tissues, according to Charles Murray, the institutes interim director. In an April 9 editorial in the Seattle Times, he writes, This year, we also seek a first-time investment from our state legislature.

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Venture capitalists are betting big on regenerative medicine, but it's ... - Quartz

At the University of Washingtons Institute for Stem Cell and Regenerative Medicine, scientists and physicians are manipulating stem cells to heal and restore the function of hearts, eyes, kidneys and other tissues.

IF you have a heart attack, hopefully youll survive. But your body will be forever changed. The worlds best doctors cant undo the damage; instead, drugs and devices will help you live with a heart whose function too often dwindles.

The body cannot replace muscle cells that die in heart attacks maladies that help make heart failure the No. 1 global cause of death and our nations biggest health care expense. These patients face daily medication, decreased energy and, for the lucky 0.1 percent, the ability to qualify for an extraordinarily costly heart transplant and anti-rejection medication that also leaves them more vulnerable to other diseases.

Thanks to medical advances, heart failure has become a chronic condition that people are now managing for decades. The same is true for diabetes, kidney disease and arthritis. But with that longevity comes a tether to drug regimens whose costs rise seemingly at whim.

Dr. Charles Murry is interim director of UW Medicines Institute for Stem Cell and Regenerative Medicine.

These chronic diseases are a major reason that health-care costs hold center stage in Americans consciousness.

Amid our collective uncertainty, medical science offers one path of relief. Specifically, the engineering of human cells and tissues to restore vitality to poorly functioning organs.

The medical conditions named above share a common root not addressed by todays best care: The body is missing a population of cells that do critical work. If we could restore that population, we could cure many chronic diseases.

At the University of Washingtons Institute for Stem Cell and Regenerative Medicine (ISCRM), scientists and physicians are manipulating stem cells to heal and restore the function of hearts, eyes, kidneys and other tissues.

This year, we also seek a first-time investment from our state Legislature.

Weve pioneered techniques to grow unlimited human heart muscle cells in the lab. We were the first to transplant these cells into injured hearts and repair the injury with new tissue growth. UW Medicine will begin first-in-human tests of these cells in Seattle in 2019.

If this one and done treatment prevents heart failure in even the sickest 10 percent of heart-attack patients, our nation could save a staggering $3.5 billion per year in health-care costs. More importantly, these patients will lead longer, healthier, more productive lives.

Other ISCRM scientists are pursuing a gene therapy for muscular dystrophy, a devastating illness that often strikes young boys. The therapy, tested in Labrador puppies that were paraplegic as a result of the same, naturally occurring muscle-wasting disease, had the dogs leaping and frolicking in just weeks. A clinical trial is planned for 2018.

We are similarly probing therapies for cancer, kidney failure, diabetes and Alzheimers. And were doing this with the Northwests entrepreneurial spirit: In the past decade, ISCRM has patented 250+ discoveries with commercial potential and started 20 companies.

Legislatures in at least 11 other states, including California, New York, Wisconsin, Minnesota and Maryland, have invested cumulative billions in regenerative medicine. Most of that funding has gone to university-based research centers like ours.

To this point there has been no state investment in ISCRM. Nevertheless we have built a world-class program with federal grants and private philanthropy. But those dollars come in boom-and-bust cycles, and what we need now is stable funding to maintain competitiveness.

For this reason, the UW seeks $6 million in operating funds from the Legislature, starting with the next biennium, to recruit and retain top scientists, fund promising results at early stages, and train young researchers and clinicians.

We are grateful, at this juncture, that the state Senate included us in its initial budget.

We ask all legislators to invest in the health of our residents and in the promise of what weve accomplished so far. With stem-cell biology, we are ready to rebuild solid tissues like the heart and potentially cure our nations greatest cause of death and health-care expense.

Clinical success will make Washington a destination for heart repair and other regenerative therapies. This race is ours to lose.

Excerpt from:
Pioneering work on stem-cell therapies at UW deserves state ... - The Seattle Times

Stem cell cures are real, and more are on the way. Thats part of the message Californias stem cell agency will deliver in a special patient advocate event in La Jolla on Thursday, April 20.

To be held from noon to 1 p.m., the California Institute for Regenerative Medicine (CIRM) event will take place at the Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037. Its across the street from the Salk Institute for Biological Studies.

Stem cell experts will describe the work done and in progress with the numerous kinds of stem cells, embryonic and non-embryonic, and the public will be able to ask questions.

Those interested in attending can RSVP via the Web at j.mp/cirmsd1.

The event, Stem Cell Therapies and You, is sponsored by CIRM and UC San Diego, which hosts one of CIRMs alpha stem cell clinics.

Four speakers are to present their perspectives on stem cell research:

-- Catriona Jamieson, Director of the CIRM UC San Diego Alpha Stem Cell Clinic and an expert on blood cancers

-- Jonathan Thomas, Chair of CIRMs governing board

-- Jennifer Briggs Braswell, Executive Director of the Sanford Stem Cell Clinical Center

-- David Higgins, Patient Advocate for Parkinsons on the CIRM board

Click on the video slide show below to hear an interview with Thomas about the event:

No stem cell treatments funded by CIRM have yet been approved for use. But dozens of clinical trials with these experimental therapies are under way, and some patients have already been cured.

Most spectacularly, a number of children born with bubble baby disease, or SCID, have been cured of their immune deficiency by CIRM-funded research. Scientists extracted some of their blood-forming stem cells, repaired the genetic defect and then reinfused them into the children. The stem cells proceeded to build a functional immune system.

CIRM was given $3 billion by the states voters in a $6 billion bond issue in 2004 to develop new disease treatments with stem cells. (The remaining $3 billion represents bond interest). The agency has spent most of that money, and soon voters may be asked whether to appropriate more funding.

Do these results justify the $3 billion allocation? And do they justify more funding, whether by the state, biomedical companies or private philanthropy? Was it wise for CIRM to focus so heavily on research in its first years? (The agency was recently scrutinized by the biomedical publication Stat for funding just a trickle of clinical trials.)

And if CIRM runs out of cash, as is projected to occur by 2020, what happens to the work in progress?

These are some of the questions CIRM faces as its cash winds down over the next few years.

Thomas, the CIRM board chairman, said the event is one of a series in which CIRM presents its evidence not only to patient advocates, but to the taxpayers who fund CIRM.

This will be the first one, Thomas said. Well have one in Los Angeles, and have one in San Francisco, one in Sacramento, and maybe the Central Valley.

Well hear the latest with projects that are in clinical trials. We have 30-plus now in clinical trials, Thomas said. A great many of those are being undertaken at our alpha stem cell clinics. A prominent one of course is at UC San Diego.

So well talk about what theyre doing but also about whats happening elsewhere in the network at the other alpha stem cell clinics.

bradley.fikes@sduniontribune.com

(619) 293-1020

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Public invited to stem cell cures event in San Diego April 20 - The San Diego Union-Tribune

WASHINGTON, DC--(Marketwired - Apr 6, 2017) - The Alliance for Regenerative Medicine (ARM) today released the complete agenda for its upcoming fifth annual Cell & Gene Therapy Investor Day, taking place April 27, 2017 in Boston, MA. This event, co-hosted by Piper Jaffray and held in partnership with Cowen and Company is the only investor conference specifically focused on cell and gene therapies, offering exclusive access to the field's most promising companies.

This year's Cell & Gene Therapy Investor Day is expected to attract 350+ attendees, including 175+ active investors and analysts and will feature presentations by 30+ companies, along with panels and fireside chats by the field's foremost thought leaders.

2017 Panel Sessions and Speakers:

Fireside Chat Olivier Danos, Ph.D., Chief Scientific Officer, REGENXBIO (moderator) James M. Wilson, M.D., Ph.D., Rose H. Weiss Professor and Director, Orphan Disease Center; Professor of Medicine and Pediatrics; Director, Gene Therapy Program, Perelman School of Medicine, University of Pennsylvania

Panel I: Cell Therapy Beyond Oncology: Where Does the Greatest Potential Lie? Edward Tenthoff, Managing Director & Senior Research Analyst, Piper Jaffray (moderator) Eduardo Bravo, CEO, TiGenix Adam Gridley, President and CEO, Histogenics Paul Laikind, President and CEO, ViaCyte Chaim Lebovits, President and CEO, BrainStorm Cell Therapeutics Emile Nuwaysir, Ph.D., CEO, BlueRock Therapeutics

Panel II: Gene Therapy: Commercialization Readiness & Market Access Challenges Joshua Schimmer, M.D., Managing Director & Senior Research Analyst, Piper Jaffray (moderator) Faraz Ali, Chief Business Officer, REGENXBIO Sven Kili, M.D., VP and Head of Gene Therapy Development, GlaxoSmithKline Arthur Tzianabos, Ph.D., President and CEO, Homology Medicines Elizabeth White, Ph.D., Assistant VP, Early Commercial Planning, Rare Disease and Gene Therapy, Pfizer Innovative Health

Panel III: Immuno-Oncology: What Are the Key Issues as First Products Approach Commercialization? Timothy Schroeder, CEO, CTI Clinical Trial and Consulting (moderator) Usman Azam, M.D., President and CEO, Tmunity Therapeutics David Epstein, Executive Partner, Flagship Pioneering Rick Fair, President and CEO, Bellicum Pharmaceuticals Jeffrey Walsh, Chief Financial and Strategy Officer, bluebird bio

2017 Presenting Companies:

4D Molecular Therapeutics, Abeona Therapeutics, Adverum Biotechnologies, AGTC, Argos Therapeutics, Audentes Therapeutics, AVROBIO, BioCardia, bluebird bio, Bone Therapeutics, Caladrius Biosciences, Capricor Therapeutics, Celyad, Fate Therapeutics, Fibrocell, GenSight Biologics, Histogenics, Homology Medicines, Juventas Therapeutics, Kiadis Pharma, Lysogene, Mesoblast, MiMedx, Orchard Therapeutics, Oxford BioMedica, Pluristem Therapeutics, Precision Biosciences, ReNeuron, Sangamo Therapeutics, Semma Therapeutics, Synpromics, TiGenix, TxCell, uniQure, Vericel, and Voyager Therapeutics

In addition to the event's co-host Piper Jaffray, sponsors include Cowen and Company; Cognate BioServices; Cryoport; CTI Clinical Trial and Consulting Services; Kawasaki; Lonza; Medpace; PCT, a Caladrius Company; and Edison. For more information please visit the event's website at http://www.arminvestorday.com.

Credentialed investors and life science strategic partners can indicate their interest in attending here. Members of the media interested in attending are asked to please contact Lyndsey Scull at lscull@alliancerm.org.

The event will be held April 27, 2017, beginning at 7:30am at The State Room, 60 State Street, Boston, MA 02109.

About The Alliance for Regenerative Medicine

The Alliance for Regenerative Medicine (ARM) is an international multi-stakeholder advocacy organization that promotes legislative, regulatory and reimbursement initiatives necessary to facilitate access to life-giving advances in regenerative medicine worldwide. ARM also works to increase public understanding of the field and its potential to transform human healthcare, providing business development and investor outreach services to support the growth of its member companies and research organizations. Prior to the formation of ARM in 2009, there was no advocacy organization operating in Washington, D.C. to specifically represent the interests of the companies, research institutions, investors and patient groups that comprise the entire regenerative medicine community. Today, ARM has more than 250 members and is the leading global advocacy organization in this field. To learn more about ARM or to become a member, visit http://www.alliancerm.org.

Originally posted here:
The Alliance for Regenerative Medicine Releases Agenda for Fifth Annual Cell & Gene Therapy Investor Day - Marketwired (press release)

CANTON, Mass., April 6, 2017 /PRNewswire/ --Stem cell scientists, researchers and product developers will learn more about Organogenesis' state-of-the art manufacturing process and successful commercial-scale production of FDA-approved wound healing therapies at the 6th Stem Cell Product Development and Commercialization Conference held April 6-7 in Boston, Massachusetts. The conference highlights cutting-edge developments in all areas of stem cell research, including the biology, medicine, applications and regulation of stem cells.

Zorina Pitkin, PhD, Senior Vice President of Quality for Organogenesis, will participate in an expert panel to discuss Apligraf and Dermagraft, two bioengineered, living cell-based therapies that are produced on a commercial scale by Organogenesis. The presentation will cover the Apligraf manufacturing process and highlight the important role of keratinocyte stem cells in functional Apligraf product.

Apligraf (manufactured near the conference, in Canton, MA), and Dermagraft (manufactured in San Diego, CA), are FDA-approved Class III medical devices indicated for the treatment of diabetic foot ulcers. Apligraf is also indicated for the treatment of venous leg ulcers. More than 1 million units of the products have been shipped to date.

"One of the challenges we see with cell-based manufacturing is the transition from pilot to commercial scale production and the ability to perform large scale manufacturing at a low cost," said Dr. Pitkin. "At Organogenesis, we've achieved this successfully through process optimization and product consistency that includes multiple levels of quality control and safety."

In Apligraf, keratinocyte stem cells are required to form the product's differentiated epidermis and provide increased levels of growth factors and cytokines, so it is vital that these cells are preserved through the manufacturing, shipping and distribution process. Through a scale-up manufacturing process that creates a three-dimensional bi-layered construct, Organogenesis is able to produce a bioengineered product with living cells on a consistent basis that delivers a therapeutic benefit to patients with hard-to-heal wounds.

"With five million Americans affected by diabetic foot ulcers and venous leg ulcers, it's crucial that we consistently produce and manufacture safe, reliable products that promote healing," added Dr. Pitkin. "Organogenesis is at the forefront of this effort, having developed a successful and reliable manufacturing process."

The 6th Stem Cell Product Development and Commercialization Conference presents information regarding cutting-edge developments in all areas of stem cell research, including the biology, medicine, applications and regulation of stem cells. Topics of discussion include recent developments in pre-clinical and clinical trials of stem cell therapy, regenerative medicine and tissue engineering, cancer stem cells, immunotherapy, stem cell reprogramming, and regulatory policies regarding stem cell research.

About Organogenesis Inc.Headquartered in Canton, Massachusetts, Organogenesis Inc. is a global leader in regenerative medicine, offering a portfolio of bioactive and acellular biomaterials products in advanced wound care and surgical biologics, including orthopedics and spine. Organogenesis' versatile portfolio is designed to treat a variety of patients with repair and regenerative needs. For more information, visit http://www.organogenesis.com.

CONTACT:Angelyn Lowe (781) 830-2353 alowe@organo.com

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/organogenesis-shares-successes-and-best-practices-for-cell-based-product-manufacturing-at-the-6th-stem-cell-product-development-and-commercialization-conference-300436140.html

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Organogenesis Shares Successes and Best Practices for Cell-Based Product Manufacturing at the 6th Stem Cell ... - Yahoo Finance

His lab can grow human heart cells that beat, and today Dr. Gordon Keller, one of the world's leading stem cell scientists, brings his vision of future medical therapies to Innovation Place at the University of Saskatchewan.

The future, Keller told CBC Radio's Saskatoon Morning isn't far off. After all, he said, stem cellsare already inuse for people needing bone marrow transplants.

"That is, in essence, the gold standard of stem cell therapies," saidKeller, who is the director ofthe McEwen Centre for Regenerative Medicine in Toronto.

While the idea of growing complete new human organs may bea future dream, Keller said that introducing strong new stem cells to damaged organs is a reality.

"We can make those cells now to try and repair those damaged areas following, let's say, a heart attack areas of the brain, pieces of cartilage we can make, liver cells we can make," he said.

"We are looking at trying to create a universal donor cell that would not be rejected, so it would really be the workhorse of what we want to do."

Keller said stem cells show great promise in being able to eradicate ailments like heart diseaseandParkinson's disease.

"It'll be a game changer, if what we believe can be done works."

Keller has already been at this for decades, watching the sometimes slow progress of new medical therapies, struggling as all researchers do to find the money they need to save lives.

So what keeps him going?

"People come by the lab all the time and we show them a dish full of human heart cells that are beating. If you go into work every day and see that "

Keller is speaking at the Atrium at Innovation Place from 3:00 to 5:00 p.m. CST today.

See the article here:
Researcher brings future of medicine to Saskatoon - CBC.ca

At a scientific meeting this week, researchers report some progress in developing an immunotherapy for ovarian cancer. However, they also outline the considerable challenges that remain before the treatment can be made effective for this and other cancers that have solid tumors.

The researchers - from the Fred Hutchinson Cancer Research Center (Fred Hutch) in Seattle, WA - presented the findings at the annual meeting of the American Association of Cancer Research in Washington, D.C.

Estimates from the American Cancer Society suggest that, in the United States, around 22,440 women will be diagnosed with ovarian cancer and approximately 14,000 will die from the disease during 2017.

The cancer begins in cells of the ovaries - reproductive glands found only in women. Each woman normally has two ovaries, situated on each side of the uterus inside the pelvis. The ovaries produce eggs that travel to the uterus through the fallopian tubes. If an egg is fertilized by male sperm, it develops into a fetus.

Dr. Kristin Anderson, an immunotherapy researcher at Fred Hutch who presented the findings at the meeting, says that while ovarian cancer is not as common in the U.S. as other cancers with solid tumors, it has a low rate of survival and a high rate of relapse. The main reason is that the cancer does not cause obvious symptoms and is often advanced by the time it is diagnosed.

Immunotherapy is a relatively new area of medicine that is showing promising results in the treatment of cancer. The approach uses the patient's own immune system to fight disease.

The new study concerns a method called adoptive T cell transfer. In this approach, immune cells called T cells are taken from the patient's own blood and trained to target and destroy cancer cells. Then, after multiplying in the laboratory, the primed cells are returned to the patient's body. Sometimes donor cells are used instead.

Fast facts about ovarian cancer

Learn more about ovarian cancer

Fred Hutch have a number of teams researching immunotherapy cancer treatments. In particular, Dr. Anderson and colleagues have reported success in using adoptive T cell transfer to treat blood cancers.

In her meeting presentation, Dr. Anderson reported progress on applying lessons learned from that work to the treatment of solid tumors.

The researchers found that ovarian cancer cells overproduce two proteins - WT1 and mesothelin - and showed that T cells engineered to target them can kill mouse and human ovarian cancer cells in the laboratory.

They also found that the engineered T cells significantly increased survival in a mouse model of ovarian cancer.

However, Dr. Anderson cautions that there is still some way to go before adoptive T cell transfer is ready for clinical trials in human patients.

The team discovered that, compared with treating blood cancers, it is much harder to apply T cell therapy to solid tumors like breast, ovarian, lung, and pancreatic cancers.

In leukemia and lymphoma, the engineered T cells can be infused directly into the bloodstream to target the blood cancer. However, access to solid tumors that are tucked away inside the body poses some major challenges. Among these are issues concerning the tumor microenvironment - a mixture of noncancerous cells, molecules, and extracellular matrix in and around the tumor.

Dr. Anderson outlines three particular challenges posed by the tumor microenvironment that they are working on. One is the fact that there are cells and proteins in the tumor microenvironment that send signals to the T cells that tell them to shut down or simply ignore the tumor cells.

The team suggests that there are some existing drugs called checkpoint inhibitors that they could explore to tackle this problem. Another approach could be to engineer the T cells to block these particular signals.

The second challenge is that ovarian tumor cells and neighboring blood vessels send self-destruct signals to the T cells, causing them to commit suicide before they can attack cancer cells.

The Fred Hutch team is already working on a solution to this second challenge in the form of a fusion protein that boosts the T cells' anticancer activity when they receive these self-destruct signals.

The third challenge that the researchers have identified in the solid tumor microenvironment is the problem of low sugar. To grow as rapidly as they do, ovarian cancer cells devour sugar, which they get from their environment.

However, the engineered T cells also need this sugar to fuel their journey to, and attack on, the cancer cells. The researchers at Fred Hutch are looking for a way to engineer the T cells so that they use a different source of energy.

Dr. Anderson says that while they are currently focusing on ovarian cancer, they believe that these solutions will also help to make progress on using adoptive T cell transfer with other solid tumors.

"If we can solve some of the issues that really plague us with these hard ones, then we can more readily apply [the solutions] to cancers that have fewer of these hurdles," she explains, as she concludes:

"Tumor microenvironment issues come hand-in-hand with working on solid tumors."

The team hopes to start a human clinical trial of adoptive T cell transfer for ovarian cancer in the next few years.

Learn about 12 newly discovered genetic variants that raise the risk of ovarian cancer.

The rest is here:
Ovarian cancer: Effective immunotherapy steps closer with new T ... - Medical News Today

Until now, researchers have focused only on identifying these types of single-lineage repressors, said Wernig. The concept of an everything but repressor is entirely new.

In 2010, Wernig showed that it is possible to convert skin cells into functional neurons over the course of three weeks by exposing them to a combination of just three proteins that are typically expressed in neurons. This direct reprogramming bypassed a step called induced pluripotency that many scientists had thought was necessary to transform one cell type into another.

One of the proteins necessary to accomplish the transformation of skin to neurons was Myt1l. But until this study the researchers were unaware precisely how it functioned.

Usually we think in terms about what regulatory programs need to be activated to direct a cell to a specific developmental state, said Wernig. So we were surprised when we took a closer look and saw that Myt1l was actually suppressing the expression of many genes.

These genes, the researchers found, encoded proteins important for the development of lung, heart, liver, cartilage and other types of non-neuronal tissue. Furthermore, two of the proteins, Notch and Wnt, are known to actively block neurogenesis in the developing brain.

Blocking Myt1l expression in the brains of embryonic mice reduced the number of mature neurons that developed in the animals. Furthermore, knocking down Myt1l expression in mature neurons caused them to express lower-than-normal levels of neural-specific genes and to fire less readily in response to an electrical pulse.

Wernig and his colleagues contrasted the effect of Myt1l with that of another protein called Ascl1, which is required to directly reprogram skin fibroblasts into neurons. Ascl1 is known to specifically induce the expression of neuronal genes in the fibroblasts.

Together, these proteins work as a perfect team to funnel a developing cell, or a cell that is being reprogrammed, into the desired cell fate, said Wernig. Its a beautiful scenario that both blocks the fibroblast program and promotes the neuronal program. My gut feeling would be that there are many more master repressors like Myt1l to be found for specific cell types, each of which would block all but one cell fate.

Wernig is a member of Stanfords Cardiovascular Institute, Child Health Research Institute, Cancer Institute, Neurosciences Institute and Bio-X.

Other Stanford co-authors of the paper are postdoctoral scholars Soham Chanda, PhD, Bo Zhou, PhD, Xuecai Ge, PhD, and Philip Brennecke, PhD; graduate students Cheen Ang, Thomas Vierbuchen and Daniel Fuentes; research assistant Sarah Grieder; undergraduate student Brandon Walker; professor of genetics Lars Steinmetz, PhD; and professor of molecular and cellular biology Thomas Sudhof, MD.

The research was supported by the German Research Foundation, the National Institutes of Health (grant R01MH092931), the California Institute for Regenerative Medicine, the New York Stem Cell Foundation, the Howard Hughes Medical Institute, the Swedish Research Council, the Swedish Government Initiative for Strategic Research Institute, the Department of Health and Human Services and Spectrum Child Health.

Stanfords Department of Pathology also supported the work.

More:
Nerve cells actively repress alternative cell fates | News Center ... - Stanford Medical Center Report

April 5, 2017 Susan Bonner-Weir, Ph.D., is Senior Investigator in the Islet Cell And Regenerative Biology Section at Joslin Diabetes Center, and Professor of Medicine at Harvard Medical School. Credit: John Soares

Diabetes researchers have puzzled for decades about why insulin-producing beta cells in one pancreatic islet often look and behave quite differently than their counterparts in the same islet or in nearby islets. Using newly identified cellular markers of aging, Joslin Diabetes Center scientists now have shown that this diversity may be driven at least in part by differently aged beta cell populations within the pancreas.

Additionally, the Joslin team demonstrated that the aging of beta cells, with associated losses of their insulin secretion, can be accelerated by insulin resistance, a condition that can lead toward type 2 diabetes.

"This research opens up an entirely new set of questions about the development of type 2 diabetes," says Susan Bonner-Weir, a Joslin Senior Investigator and corresponding author on a paper describing the work in the journal Cell Metabolism. The disease worsens over time as beta cells die off or perform less effectively, for reasons that are not well understood.

Scientists have long known that beta cells change significantly over time, says Bonner-Weir, who is also Professor of Medicine at Harvard Medical School (HMS). Back in 2011, for example, her lab demonstrated that beta cells in newborn rats are immature cells with very different gene expression and function than adult beta cells.

Her lab's most recent work, led by HMS Instructor Cristina Aguayo-Mazzucato, started instead with very old mice, created for another experiment, whose beta cells emitted fluorescent signals. The investigators could compare the insulin-producing beta cells from these mice with those from younger, genetically identical mice to examine the characteristics of the cells across the mouse lifespan.

As they did so, Aguayo-Mazzucato and her colleagues were struck by dramatic difference in the genes expressed by beta cells in animals of various ages. The researchers followed up to identify markers of aging in these cells, using several mouse modelsone with impaired glucose tolerance (a contributor to type 2 diabetes progression) and another that shows markers of rapid aging.

The scientists identified several markers of aging beta cells, including one protein called IGF1R that is an important player in cell survival. The markers highlighted the striking diversity of beta cell aging, and functional decline, both within and between islets in both mouse and human pancreases.

This diversity of age among beta cells may be responsible at least in part for the striking heterogeneity that has been observed in both mice and humans. "We showed that this heterogeneity may be based on different populations of different-aged beta cells," Bonner-Weir says. "Even in young animals, where many beta cells are still immature, you may have other beta cells that are at the end of their lifespan. Each life stage may have a different phenotype (different gene expression and function) than the other stages."

The heterogeneity may reflect typical lifespans of these cells. "There's a lot of growth in beta cells up until puberty or even young adulthood, but after that, there's a very slow turnover," she says. "A few cells reach the end of their life span and die, and a few other cells are created."

The Joslin team went on to study the effect of metabolic stress on signs of aging. In one set of experiments, when the scientists boosted insulin resistance by giving mice a compound that cuts insulin signaling, they saw increased expression of several markers of aging in beta cells.

In another effort, examining human pancreas specimens, the scientists found that two of the aging markers were significantly increased among people with type 2 diabetes. The researchers also detected surprising numbers of aged beta cells in people as young as 20.

"We will follow up using more human islets and trying to understand how many of these functions translate from animal models to humans," says Bonner-Weir, who notes that human islets are far more diverse than those in lab animals.

Her group also will probe further into their findings, including pinpointing factors that boost aging in beta cells, examining whether this aging is reversible and finding potential ways to reduce related metabolic stresses.

Additionally, the Joslin team will study why nearby pancreatic islets can display such dramatic differences in beta cell aging. One hypothesis is that beta cells in some islets may remain dormant until needed, and thus not age as quickly, Bonner-Weir says. Another, more controversial, is that new islets may grow in new pancreatic lobes appearing in adulthood.

The research also may help to suggest answers to some puzzles in type 1 diabetes, she says, including why some cells seem to be more resistant to the autoimmune attack that causes the disease and how beta cells can be found in some people who have had the condition for decades.

Explore further: New type of insulin-producing cell discovered

More information: Cristina Aguayo-Mazzucato et al, Cell Aging Markers Have Heterogeneous Distribution and Are Induced by Insulin Resistance, Cell Metabolism (2017). DOI: 10.1016/j.cmet.2017.03.015

In people with type I diabetes, insulin-producing beta cells in the pancreas die and are not replaced. Without these cells, the body loses the ability to control blood glucose. Researchers at the University of California, ...

If you become resistant to insulin, a condition that is a precursor to type 2 diabetes, your body tries to compensate by producing more of the "beta" cells in the pancreas that produce the critical hormone. Researchers have ...

A Yale-led research team identified how insulin-producing cells that are typically destroyed in type 1 diabetes can change in order to survive immune attack. The finding may lead to strategies for recovering these cells in ...

Joslin researchers have identified immune cells that promote growth of beta cells in type 1 diabetes. This study provides further evidence of a changed role for immune cells in type 1 diabetes pathology. The study appears ...

Researchers at the Ume Center for Molecular Medicine have created the first 3D spatial visualization of an obese mouse pancreas showing the distribution dynamics of insulin producing beta cells. The results show significant ...

Eating a high fat and high sugar diet when pregnant leads to metabolic impairments in both the mother and her unborn child, which may "program" them for potential health complications later in life, researchers have shown.

Diabetes researchers have puzzled for decades about why insulin-producing beta cells in one pancreatic islet often look and behave quite differently than their counterparts in the same islet or in nearby islets. Using newly ...

Research led by the University of Otago, Wellington has found that a 'home-grown' naturally occurring probiotic reduces the risk of developing diabetes during pregnancy (gestational diabetes) and lowers fasting blood sugar.

Americans of South Asian descent are twice as likely as whites to have risks for heart disease, stroke and diabetes, when their weight is in the normal range, according to a study headed by Emory University and UC San Francisco.

Scientists may have found a new tool for studyingand maybe even treatingType 2 diabetes, the form of diabetes considered responsible for close to 95 percent of cases in the United States.

With a series of new grants, Saint Louis University researchers will tackle the twin epidemics of diabetes and obesity by tapping into the potential of two nuclear receptors that control muscle metabolism. The scientists ...

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In what's reported to be a world-first, last Tuesday, a Japanese man received a pioneering retinal cell transplant grown from donor stem cells instead of his own.

Doctors took skin cells from a donor bank and reprogrammed them into induced pluripotent stem (iPS) cells, which can be coaxed to grow into most cell types in the body.

For this procedure, the physicians grew the iPS cells into atype of retinal cell, and then injected them into the retina of the patient's right eye.

The test subject was a man in his 60s who has been living with age-related macular degeneration-a currently incurable eye disease that slowly leads to loss of vision.

If this news sounds somewhat familiar, it's because the same team of Japanese doctors successfully performed a similar transplant in 2014. But in that case, the iPS cells came from the patient's own skin, not from a donor.

The 2014 treatment involved culturing a patient's cells into a thin sheet of retinal pigment epithelium cells, which they transplanted directly under her retina.

One year later, their results showed that the patient's disease had not progressedas it would have without any treatment, and she continues to do well.

But a second case study after the 2014 success never went ahead - the researchers found genetic abnormalities in the iPS cells they had derived from an additional patient's skin. To avoid complications, the doctors fromRIKENand Kobe City Medical Centre General Hospital decided to halt the trial and refine their approach.

Now they are back with a potentially safer technique that uses cells from a donor bank. The patient who received the transplant last week is the first of five approved for a study by Japan's health ministry in February this year. It's important to note that so far this is a safety study - a precursor to a clinical trial.

As team leader Masayo Takahashi from RIKEN told a press conference, we will have to wait and see for several years until we know for sure whether last week's transplant was a complete success - which is the whole point of doing a safety study like this.

"A key challenge in this case is to control rejection. We need to carefully continue treatment," she said.

The patient will be closely observed for a year, and then receive check-ups for three more years. The main things for the team to look out for are rejection of the new retinal cells, and the development of potential abnormalities.

An editorial in Nature praises the team's cautious approach, emphasising that this work with iPS cells could pave a smoother path for other trials in the emerging field of stem cell medicine.

If donor cells turn out to be a viable option in iPS cell procedures, it would be huge for creating more affordable stem cell treatments that anyone can benefit from.

Instead of having to induce stem cells out of each individual patient's samples, doctors could go down the cheaper and quicker route of simply picking a suitable match from a donor bank.

Stem cell treatments such as this new procedure are an extremely promising avenue in medicine, but scientists are right to remain cautious and proceed slowly. Just last month a devastating case report broke the news that three women lost their eyesight by participating in a dodgy stem cell trial.

On the other hand, in 2015, an experimental stem cell treatment showed promise in multiple sclerosis (MS) patients, and just last year, stem cell injections were used to help stroke patients in recovery.

With all these exciting developments, we'll definitely be keeping an eye on further reports from the Japanese team.

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A Japanese man just got another person's stem cells transplanted in ... - ScienceAlert