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Cardiac stem cells rejuvenate rats’ aging hearts, study says – CNN

By NEVAGiles23

The old rats appeared newly invigorated after receiving their injections. As hoped, the cardiac stem cells improved heart function yet also provided additional benefits. The rats' fur fur, shaved for surgery, grew back more quickly than expected, and their chromosomal telomeres, which commonly shrink with age, lengthened.

The old rats receiving the cardiac stem cells also had increased stamina overall, exercising more than before the infusion.

"It's extremely exciting," said Dr. Eduardo Marbn, primary investigator on the research and director of the Cedars-Sinai Heart Institute. Witnessing "the systemic rejuvenating effects," he said, "it's kind of like an unexpected fountain of youth."

"We've been studying new forms of cell therapy for the heart for some 12 years now," Marbn said.

Some of this research has focused on cardiosphere-derived cells.

"They're progenitor cells from the heart itself," Marbn said. Progenitor cells are generated from stem cells and share some, but not all, of the same properties. For instance, they can differentiate into more than one kind of cell like stem cells, but unlike stem cells, progenitor cells cannot divide and reproduce indefinitely.

Since heart failure with preserved ejection fraction is similar to aging, Marbn decided to experiment on old rats, ones that suffered from a type of heart problem "that's very typical of what we find in older human beings: The heart's stiff, and it doesn't relax right, and it causes fluid to back up some," Marbn explained.

He and his team injected cardiosphere-derived cells from newborn rats into the hearts of 22-month-old rats -- that's elderly for a rat. Similar old rats received a placebo injection of saline solution. Then, Marbn and his team compared both groups to young rats that were 4 months old. After a month, they compared the rats again.

Even though the cells were injected into the heart, their effects were noticeable throughout the body, Marbn said

"The animals could exercise further than they could before by about 20%, and one of the most striking things, especially for me (because I'm kind of losing my hair) the animals ... regrew their fur a lot better after they'd gotten cells" compared with the placebo rats, Marbn said.

The rats that received cardiosphere-derived cells also experienced improved heart function and showed longer heart cell telomeres.

Why did it work?

The working hypothesis is that the cells secrete exosomes, tiny vesicles that "contain a lot of nucleic acids, things like RNA, that can change patterns of the way the tissue responds to injury and the way genes are expressed in the tissue," Marbn said.

It is the exosomes that act on the heart and make it better as well as mediating long-distance effects on exercise capacity and hair regrowth, he explained.

Looking to the future, Marbn said he's begun to explore delivering the cardiac stem cells intravenously in a simple infusion -- instead of injecting them directly into the heart, which would be a complex procedure for a human patient -- and seeing whether the same beneficial effects occur.

Dr. Gary Gerstenblith, a professor of medicine in the cardiology division of Johns Hopkins Medicine, said the new study is "very comprehensive."

"Striking benefits are demonstrated not only from a cardiac perspective but across multiple organ systems," said Gerstenblith, who did not contribute to the new research. "The results suggest that stem cell therapies should be studied as an additional therapeutic option in the treatment of cardiac and other diseases common in the elderly."

Todd Herron, director of the University of Michigan Frankel Cardiovascular Center's Cardiovascular Regeneration Core Laboratory, said Marbn, with his previous work with cardiac stem cells, has "led the field in this area."

"The novelty of this bit of work is, they started to look at more precise molecular mechanisms to explain the phenomenon they've seen in the past," said Herron, who played no role in the new research.

One strength of the approach here is that the researchers have taken cells "from the organ that they want to rejuvenate, so that makes it likely that the cells stay there in that tissue," Herron said.

He believes that more extensive study, beginning with larger animals and including long-term followup, is needed before this technique could be used in humans.

"We need to make sure there's no harm being done," Herron said, adding that extending the lifetime and improving quality of life amounts to "a tradeoff between the potential risk and the potential good that can be done."

Capicor hasn't announced any plans to do studies in aging, but the possibility exists.

After all, the cells have been proven "completely safe" in "over 100 human patients," so it would be possible to fast-track them into the clinic, Marbn explained: "I can't tell you that there are any plans to do that, but it could easily be done from a safety viewpoint."

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The unexpected role of a well-known gene in creating blood – Medical Xpress

By NEVAGiles23

The early heart tube of a chick embryo: cardiac and endothelial cells are made visible by specifically expressing fluorescent proteins under the control of the Nkx2.5 (green) and Isl1 (red) cardiovascular genes. Credit: Weizmann Institute of Science

One of the first organ systems to form and function in the embryo is the cardiovascular system: in fact, this developmental process starts so early that scientists still have many unresolved questions on the origin of the primitive heart and blood vessels. How do the first cells the progenitors that are destined to become part of this system participate in shaping the developed cardiovascular system?

Dr. Lyad Zamir, a former PhD student in the lab of Prof. Eldad Tzahor in the Weizmann Institute of Science's Department of Molecular Cell Biology, developed a method to image the earliest cardiovascular progenitors and track them and their descendants through the developing embryo in real time. His movies took place in fertilized chicken eggs, in which a complex network of blood vessels forms within the yolk sac to nourish the embryo. The findings of this research were recently published in eLife.

Working in collaboration with the lab of Prof. Richard Harvey of the Victor Chang Cardiac Research Institute and the University of New South Wales, both in Australia, Prof. Tzahor and Dr. Zamir focused on a gene called Nkx2-5. This gene encodes a transcription factor, which is a regulatory protein that controls the expression of other genes involved in the development of the heart. "The new study revealed that Nkx2-5, independently of its role in the development of the heart, plays a central role in the genesis of the very first blood vessels and indeed the formation of blood," says Prof. Tzahor.

Looking at the onset of Nkx2-5 expression, the team revealed the existence of progenitor cells called hemangioblasts. These cells give rise to both the blood and vascular progenitor cells those that lead to the formation of blood vessels. These unique cells are created from the mesoderm the middle layer of cells that appears in the very early developing embryo. Researchers have been hotly debating the existence of hemangioblasts and, if they do exist, their possible function.

In the chick embryo films, the researchers could see the hemangioblasts moving to create "blood islands," which form within the primitive embryonic vessels. The researchers were surprised to observe that some of the hemangioblast cells were moving into the heart, where they formed blood stem cells. This helped make sense of other studies revealing that the early heart tube contains cells that appear to assist in generating blood cells. The researchers also identified specialized Nkx2-5-expressing cells within the lining of the newly formed aorta, where they appeared to "bud off" to produce new blood cells. Later on in development, these specialized cells move into the liver, where they give rise to the blood-forming stem cells in the fetus.

Prof. Tzahor: "Even 20 years after one of the 'master genes' for heart development was discovered, we have managed to write a new story about its action, showing that it works briefly at a very early stage in development in the formation of vessels and blood before the main action takes place in the heart. We have provided solid evidence for the existence of these very early cells and their contribution to heart and vascular development."

Because these findings reveal the early origins of at least some of the blood-forming stem cells in the embryo, they may be especially helpful in research into diseases affecting the cardiovascular system.

Explore further: Kidney research leads to surprising discovery about how the heart forms

More information: Lyad Zamir et al. Nkx2.5 marks angioblasts that contribute to hemogenic endothelium of the endocardium and dorsal aorta, eLife (2017). DOI: 10.7554/eLife.20994

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Restoring loss: Bio-inspired materials give boost to regenerative medicine – Arizona State University

By JoanneRUSSELL25

August 15, 2017

What if one day, we could teach our bodies to self-heal like a lizards tail, and make severe injury or disease no more threatening than a paper cut?

Or heal tissues by coaxing cells to multiply, repair or replace damaged regions in loved ones whose lives have been ravaged by stroke, Alzheimers or Parkinsons disease?

Such is the vision, promise and excitement in the burgeoning field of regenerative medicine, now a major ASU initiative to boost 21st-century medical research discoveries.

ASU Biodesign Institute researcher Nick Stephanopoulos is one of several rising stars in regenerative medicine. In 2015, Stephanopoulos, along with Alex Green and Jeremy Mills, were recruited to the Biodesign Institutes Center for Molecular Design and Biomimetics (CMDB), directed by Hao Yan, a world-recognized leader in nanotechnology.

One of the things that that attracted me most to the ASU and the Biodesign CMDB was Haos vision to build a group of researchers that use biological molecules and design principles to make new materials that can mimic, and one day surpass, the most complex functions of biology, Stephanopoulos said.

I have always been fascinated by using biological building blocks like proteins, peptides and DNA to construct self-assembled structures, devices and materials, and the interdisciplinary and highly collaborative team in the CMDB is the ideal place to put this vision into practice.

Yans research center uses DNA and other basic building blocks to build their nanotechnology structures only at a scale 1,000 times smaller than the width of a human hair.

Theyve already used nanotechnology to build containers to specially deliver drugs to tissues, build robots to navigate a maze or nanowires for electronics.

To build a manufacturing industry at that tiny scale, their bricks and mortar use a colorful assortment of molecular Legos. Just combine the ingredients, and these building blocks can self-assemble in a seemingly infinite number of ways only limited by the laws of chemistry and physics and the creative imaginations of these budding nano-architects.

The goal of the Center for Molecular Design and Biomimetics is to usenatures design rulesas an inspiration in advancing biomedical, energy and electronics innovation throughself-assembling moleculesto create intelligent materials for better component control and for synthesis intohigher-order systems, said Yan, who also holds the Milton Glick Chair in Chemistry and Biochemistry.

Prior to joining ASU, Stephanopoulos trained with experts in biological nanomaterials, obtaining his doctorate with the University of California Berkeleys Matthew Francis, and completed postdoctoral studies with Samuel Stupp at Northwestern University. At Northwestern, he was part of a team that developed a new category of quilt-like, self-assembling peptide and peptide-DNA biomaterials for regenerative medicine, with an emphasis in neural tissue engineering.

Weve learned from nature many of the rules behind materials that can self-assemble. Some of the most elegant complex and adaptable examples of self-assembly are found in biological systems, Stephanopoulos said.

Because they are built from the ground-up using molecules found in nature, these materials are also biocompatible and biodegradable, opening up brand-new vistas for regenerative medicine.

Stephanopoulos tool kit includes using proteins, peptides, lipids and nucleic acids like DNA that have a rich biological lexicon of self-assembly.

DNA possesses great potential for the construction of self-assembled biomaterials due to its highly programmable nature; any two strands of DNA can be coaxed to assemble to make nanoscale constructs and devices with exquisite precision and complexity, Stephanopoulos said.

During his time at Northwestern, Stephanopoulos worked on a number of projects and developed proof-of-concept technologies for spinal cord injury, bone regeneration and nanomaterials to guide stem cell differentiation.

Now, more recently, in a new studyin Nature Communications, Stephanopoulos and his colleague Ronit Freeman in the Stupp laboratory successfully demonstrated the ability to dynamically control the environment around stem cells, to guide their behavior in new and powerful ways.

In the new technology, materials are first chemically decorated with different strands of DNA, each with a unique code for a different signal to cells.

To activate signals within the cells, soluble molecules containing complementary DNA strands are coupled to short protein fragments, called peptides, and added to the material to create DNA double helices displaying the signal.

By adding a few drops of the DNA-peptide mixture, the material effectively gives a green light to stem cells to reproduce and generate more cells. In order to dynamically tune the signal presentation, the surface is exposed to a soluble single-stranded DNA molecule designed to grab the signal-containing strand of the duplex and form a new DNA double helix, displacing the old signal from the surface.

This new duplex can then be washed away, turning the signal off. To turn the signal back on, all that is needed is to now introduce a new copy of single-stranded DNA bearing a signal that will reattach to the materials surface.

One of the findings of this work is the possibility of using the synthetic material to signal neural stem cells to proliferate, then at a specific time selected by the scientist, trigger their differentiation into neurons for a while, before returning the stem cells to a proliferative state on demand.

One potential use of the new technology to manipulate cells could help cure a patient with neurodegenerative conditions like Parkinsons disease.

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Stem Cell Transplant Program Celebrates First Year – Newswise (press release)

By Dr. Matthew Watson

Newswise The University of New Mexico Comprehensive Cancer Center began helping New Mexicans with blood disorders a little more than one year ago. Since then, more than 30 New Mexicans have received treatment. Program Director Matthew Fero, MD, FACP, started the program after moving to New Mexico from the Fred Hutchinson Cancer Center in Seattle, Wash.

The UNM Comprehensive Cancer Center program is the states only bone marrow transplant program. It includes a nurse manager, nurse coordinator, a social worker, a pharmacist, infusion nurses, and an inpatient team. Bone marrow transplantation needs a multidisciplinary team because of the complexity in coordinating care, says Fero. The teams Nurse Manager, Maria Limanovich, says the team follows each person from the beginning of bone marrow transplant treatment through completion. According to Fero, the program is growing and is in the process of hiring two more doctors and an advanced practice provider.

The UNM Bone Marrow Transplant program offers treatment choices for people with lymphoma and myeloma and will expand to help people with other blood disorders. Almost 1,000 New Mexicans receive a blood cancer diagnosis each year, according to American Cancer Society estimates.

Fero and his team currently perform autologous transplants. Autologous bone marrow transplantation is the process of taking bone marrow stem cells out of a patient and then infusing them back in after the patient receives high dose therapy, says Fero. This allows us to use treatments that would otherwise harm the bone marrow.

Bone marrow, the soft reddish material that fills the inside of our bones, produces millions of new blood cells each second. These millions of cells come from a tiny number of bone marrow stem cells. These stem cells are special because they can mature into all of the different types of cells in the blood. These are the cells doctors collect for a transplant.

Because bone marrow is a liquid organ, Fero says, it can pass through an IV [intravenous] line. Doctors rarely need to take stem cells directly out of the bone, Fero explains. They use drugs to coax bone marrow stem cells into the bloodstream. From there, the blood travels through an IV line into an apheresis machine that sorts the stem cells out and returns the rest of the blood. The experience is like donating blood at a blood bank.

Once stem cells are safely stored out of the bloodstream, doctors use high-dose chemotherapy to eradicate the remaining cancer. When chemotherapy is out of their system, the patients stem cells are reinfused. The reinfusion process is similar to a blood transfusion. Once reinfused, stem cells find their way back to bone marrow where they begin to grow and make new blood cells.

Autologous bone marrow transplants are standard treatments for lymphoma and myeloma. This treatment works very well against aggressive lymphomas. In this case the goal is to cure the disease, says Fero. Autologous bone marrow transplants extend the lives of people with myeloma and gives them a better quality of life, too. Fero says, Were offering another option for their treatment.

Matthew Fero, MD, FACP, is a Professor in the Department of Internal Medicine, Division of Hematology/Oncology, at the UNM School of Medicine. He serves as Director of the Bone Marrow Stem Cell Program at the UNM Comprehensive Cancer Center. Dr. Fero received his medical degree from the University of California, Irvine, and completed his residency in Internal Medicine at the Mayo Graduate School of Medicine. He completed a medical fellowship in Medical Oncology at University of Washington and a research fellowship at Fred Hutchinson Cancer Research Center. He is a member of the American Society of Hematology and the American Society for Blood and Marrow Transplantation, and is a Fellow of the American College of Physicians. His research focuses on the molecular bases of cancer and translating new technologies into improved cancer diagnostics and novel therapies.

The University of New Mexico Comprehensive Cancer Center is the Official Cancer Center of New Mexico and the only National Cancer Institute-designated Cancer Center in a 500-mile radius. Its 125 board-certified oncology specialty physicians include cancer surgeons in every specialty (abdominal, thoracic, bone and soft tissue, neurosurgery, genitourinary, gynecology, and head and neck cancers), adult and pediatric hematologists/medical oncologists, gynecologic oncologists, and radiation oncologists. They, along with more than 500 other cancer healthcare professionals (nurses, pharmacists, nutritionists, navigators, psychologists and social workers), provided cancer care for nearly 60 percent of the adults and children in New Mexico affected by cancer. They treated 11,249 patients in 84,875 ambulatory clinic visits in addition to in-patient hospitalizations at UNM Hospital. These patients came from every county in the State. More than 12 percent of these patients participated in cancer clinical trials testing new cancer treatments and 35 percent of patients participated in other clinical research studies, including tests of novel cancer prevention strategies and cancer genome sequencing. The 130 cancer research scientists affiliated with the UNMCCC were awarded almost $60 million in federal and private grants and contracts for cancer research projects and published 301 high quality publications. Promoting economic development, they filed more than 30 new patents in FY16, and since 2010, have launched 11 new biotechnology start-up companies. Scientists associated with the UNMCCC Cancer Control & Disparities have conducted more than 60 statewide community-based cancer education, prevention, screening, and behavioral intervention studies involving more than 10,000 New Mexicans. Finally, the physicians, scientists and staff have provided education and training experiences to more than 230 high school, undergraduate, graduate, and postdoctoral fellowship students in cancer research and cancer health care delivery. Learn more at http://www.cancer.unm.edu.

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Stem cell therapy may help knees – Citizens Voice

By JoanneRUSSELL25

Q: I read that you can use your own stem cells to rejuvenate worn-out knees. Does this really work?

A: Worn out is a good way to term what happens to the knee joint with prolonged use. Lets look at how this happens, starting with cartilage.

The lower portion of the knee joint (at the tibia) contains shock absorbers called menisci made of cartilage. You have one on the inner portion and another on the outer portion of each knee. The upper portion of the knee joint (at the femur) is lined with cartilage as well. All of this cartilage helps protect the bones at the joint but it doesnt heal or regenerate well due to limited blood supply. When severe, worn cartilage leads to arthritis of the knee. In knee X-rays of people over age 60, 37 percent have shown evidence of arthritis of the knees.

The intriguing thing about stem cells is that they have the ability to become any type of cell that the body needs. The cells used for stem cell injections in the knees are called mesenchymal stem cells, and they can differentiate into bone, fat or cartilage cells. These stem cells can come from the fat cells of your body, from your bone marrow or from the inner lining of your knee joint; theyre then replicated in the laboratory and injected into the knee joint.

Heres what the research shows so far.

In a 2013 study, 32 patients with meniscal tears of the knee were injected with a combination of stem cells, platelet-rich plasma and hyaluronic acid. The study reported improved symptoms and even MRI evidence of meniscal cartilage regeneration.

In a 2014 study, 55 patients who had surgery for meniscal tears of the knees were separated into three groups, with two of the groups receiving stem cell injections. Researchers found that, after six weeks, pain had decreased substantially in the two groups that received stem cell injections and that the decrease was even greater at one and two years after the injection.

In a 2017 study in the British Journal of Sports Medicine, researchers analyzed six studies that used stem cells for osteoarthritis of the knees. In five of the studies, stem cells were given after surgery to the knee; in the other study, stem cells from a donor were administered without surgery. All the studies showed reduced pain and improved knee function. Further, in three of the four trials, MRIs corroborated the cartilage improvements.

There may be benefit to stem cell injections for cartilage loss of the knees, but more data are needed. Id also like to see more data on this type of therapy as a preventive measure for younger patients before their knees are worn out.

ASK THE DOCTORS is written by Robert Ashley, M.D., Eve Glazier, M.D., and Elizabeth Ko, M.D. Send questions to askthedoctors@

mednet.ucla.edu, or write: Ask the Doctors, c/o Media Relations, UCLA Health, 924 Westwood Blvd., Suite 350, Los Angeles, CA, 90095.

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Roswell Park-Led Analysis Shows Survival Benefit of Lenalidomide Maintenance Therapy Following Transplant – Benzinga

By daniellenierenberg

New research analysis published in JCO definitively shows an overall survival benefit from ongoing treatment with lenalidomide for patients with multiple myeloma who have already received bone marrow transplant.

Buffalo, NY (PRWEB) August 15, 2017

The first study to report that overall survival was extended for patients receiving lenalidomide as maintenance treatment for multiple myeloma has been completed, with the team's findings now published online ahead of print in the Journal of Clinical Oncology, or JCO. Philip L. McCarthy, MD, Director of the Blood and Marrow Transplant Program at Roswell Park Cancer Institute, was principal investigator for one of the three clinical studies that are reported in this updated analysis, and is first author of the publication that compiles the international team's findings and analysis.

The new study is a "meta-analysis" reporting updated findings from three large randomized, controlled clinical trials conducted in the U.S., France and Italy by the Alliance for Clinical Trials in Oncology (formerly CALGB), Intergroupe Francophone du Mylome (IFM) and Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA), respectively. The research team compared outcomes for 605 patients with newly diagnosed multiple myeloma who were treated with continuous lenalidomide (brand name Revlimid) following autologous hematopoietic stem cell transplant, also known as bone marrow transplant, and 604 patients who received either a placebo or no maintenance at all.

The meta-analysis has allowed the team to evaluate for the first time, across all three studies, whether overall survival improved for patients receiving long-term treatment with oral lenalidomide following stem cell transplant.

At seven years of observation, the authors report, 62% of those treated with maintenance lenalidomide had survived, compared to 50% of those in the control group. "The use of lenalidomide maintenance for transplantation-eligible patients can be considered a standard of care," they write, noting recent refinements that have improved the efficacy of pre-transplant induction chemotherapy and autologous stem cell transplant.

"With this complete and mature data from three large multinational studies, we now have clear evidence that ongoing treatment with lenalidomide can prevent disease progression and extend survival in patients with multiple myeloma who've received a stem cell transplant," says Dr. McCarthy, Professor of Oncology at Roswell Park and also Professor of Internal Medicine at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo. "All the investigators wish to express enormous gratitude to the patients who took part in these trials. Many others will benefit from their role in this research."

These study results were presented in abstract form at the 52nd annual meeting of the American Society of Clinical Oncology in Chicago and the 21st Congress of the European Hematology Association, Copenhagen, Denmark, both held in June 2016, and in March 2017 at the 16th International Myeloma Workshop in Delhi, India. Earlier this year, the U.S. Food and Drug Administration and its European counterpart, the European Medicines Agency, approved use of lenalidomide as maintenance therapy for multiple myeloma patients following transplant; this study was part of the regulatory submissions for those approvals.

The new publication, "Lenalidomide Maintenance After Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: A Meta-Analysis," is available at ascopubs.org.

This press release is also available on the Roswell Park website: https://www.roswellpark.org/media/news/international-lenalidomide-trials-show-survival-benefit-maintenance-therapy-following

###

The mission of Roswell Park Cancer Institute (RPCI) is to understand, prevent and cure cancer. Founded in 1898, RPCI is one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. The Institute is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation's leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit http://www.roswellpark.org, call 1-877-ASK-RPCI (1-877-275-7724) or email askrpci(at)roswellpark.org. Follow Roswell Park on Facebook and Twitter.

For the original version on PRWeb visit: http://www.prweb.com/releases/2017/08/prweb14605233.htm

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DHK – Annie McNamara, 27, myelodysplastic syndrome, Boston, with Dr. Robert Soiffer, chief, Hematologic … – WEEI.com

By raymumme

Earlier had a guest on that protects it you might just that might we'll just talk music you know but yes I've done and yes. We have another and now I. You felt it just at the time we got her elbow and grad and out whose family owns the Portland sea dogs and I had to admit I'd bounce the first pitch up. Portland seed in their video of this hole and I thought I asked rotate another chance to sit. Her family owns the airport into dogs and there's been. Apparently I Wii I know exactly where to go to the video thank you very much day. Any back to Mary's here and and her doctor doctor Robert Zoellick for. And that any. It's 27 years old hat Milo this plastic syndrome which I have to admit. I've been sixteen of these things but that's a new one on me at I don't think effort that went before what what exactly did in tale. Yes so it's blood disorder again normally found it again. Older folks. So it was sort of rare for at 25. Year old to be diagnosed with that. But certainly shared today is a bone marrow transplant so. I mean was it meant it to Dana Farber once I found out hands. Did three rounds of chemo outpatient acting forever. An and accepting of both Americans and last June. It's as the impatient at the breakdown. That doctor cipher was my transplant doctor and tenth harbor. And doctor Roberts worked for is here and I heard you say yes when she talked about the rarity of the disease how rare is it. How he treated well itself. It's the disease that as Annie said he's much more common old people. People in the 60s80s. Very uncommon. Twenty's. He can be treated with support here medications and little dose chemotherapy when picked Poulter. When patients younger. We generally want to all Americans clause with out of bone marrow transplant mild to split will lead to keep. And it becomes very eager to treat so. Despite the rarity of the disease and he was that. Attracted the entire time she just made it head on. Did it too tough to what I have to do. I'll take the chemotherapy in the transplant her sister was her daughter which is remarkable story also that. She showed remarkable courage through the entire process in and it even knows something was wrong or you feel like how long that laughed. Tired. Too. Much. The bar. Like an appealing their I don't got a good story and that's what you're gonna carry you through the. I cannot relate to that I. But it hadn't had it takes I knew something really often action difficult. Week. So. It's late night after what happened to inch its way. Saturday Javed Ali counted that's very Massachusetts. My word and act out there. That come back. It's. It doctor Lieberman can tear your donor with your sister Molly. I assume that might have been a ten for ten match perhaps. Yes it was an exact match was awesome. Sister is a senior at the academy's actors like frank. Steamers that reflects well. Making sure to keep a schedule worked with the sisters schedule them. In between graduation. Widgets so. I was really fortunate to. Match. A week later after such a perfect. It worked out I was able to hurt at mission. And I. Speaking we transplant a year after the transplant something significant happened in your life tell us what that is and. Yes so I got engaged. Almost. Exactly here after the transplant which was pretty special. Dan my fiance was served with me through the whole ride. So it was awesome very exciting ends. Its focus on planning a wedding now wedges. And that. All of that in the past years. And he was right there was Hewitt said he knows the real deal yeah really just aren't as good as our guys. Yep it's sealed the deal. And had a question for your doctors is finding that match fortunately she had a sister without match there for the bone marrow transplant was once the match but for those who don't have sisters don't have a brother that able to do that how tricky can nappy. Will things really change over the past five to eight years the better. Twenty years ago we would only do bone marrow transplant on a patient who had eight siblings a brother or sister who matched. At about fifteen years ago we started to transplants from unrelated donors volunteers dealers. Who were able to actually provided the source of stem cells and actually good outcomes. More recently we've been able to even use half matches so even a win eight other sister does it. Match fully ten out of ten match dale said a week you actually get by with a five of ten match almost as well as we can't attempt. Our friend Tara who's going to be here tomorrow had her bone marrow transplant in November. And I know she was kind of isolated for about nine months I assume you've had a similar sort of regiment you had to go through. Yes of the first hundred days I was inside you know sort of contact them on in the outside world besides my family. So I was definitely tough and then. I work for an Austin Co. act Clijsters and so I was able to work from home through the spring. And they were awesome. Sort of helping me get through flu season because my immune system. Receivers susceptible to catching something. So yeah I was you know at home until April. Answered just get getting back in readjusted to you. I. It's a real family affair doc watched any buyers Oprah folks beyonc really all came together it. That'll give her support of actually help keep healthy. A community effort. When's the wedding I'd accept. If congratulations a couple of things that couples swapping one you do work out some companies how to increase in credit out of great Fredricka. And secondly in the scouting reports and future sea dogs that we should be looking out or. Bully doesn't devers Africans as loyal you know he's doing pretty well. Commandant and the obviously. I don't have a scouting report right now but I'm sure things. You're in the nickel you need a great little bull market. Yeah it's I'd love going up there and Ankara practice hitting get a chance to. Endeavour's much he was there are very now really kind of scooted through town and yes. Now he's here hitting home runs things like every every game every other game. We took into been intently from you two's yeah. Yeah I'm not a you've got your children to this point yes it's critical to see them say it. Progress. It's to fat cats watch. Well it's great to visit with both of you and MacNamara fallible Malone multi faceted. Can not just in case you didn't hear ripped up. And doctor Robert Lichter thanks you guys that are very much for coming in it's great people that it. Thanks for having classy guys into the past. Thank you thank you and good luck with a wedding thank you and I hear from September whenever that is good luck. Think it's.

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DHK - Annie McNamara, 27, myelodysplastic syndrome, Boston, with Dr. Robert Soiffer, chief, Hematologic ... - WEEI.com

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Anika (ANIK) Grows in Orthopedic Medicines on Positive Data – Nasdaq

By NEVAGiles23

Anika Therapeutics, Inc. ANIK , a global medical technology company, specializing on integrated orthopedics medicines , has made a development with its proprietary hyaluronic acid (HA) technology. The company recently published favorable data on evaluating the usefulness of HYALOFAST, a non-woven biodegradable HA-based scaffold for treatment of cartilage lesions of the knee joint.

The study was based on 40 patients with full thickness cartilage lesions of the knee joint. 20 among them were aged above 45 and the remaining, below the figure. Per the company, all patients were implanted with HYALOFAST, soaked in bone marrow aspirate concentrate (BMAC), containing mesenchymal stem cells (MSCs) and prospectively evaluated for four years.

Data from the trial demonstrated that treatment outcomes were equally effective for both the age groups. This is more encouraging for the fact that it is difficult to treat patients above 45 years of age with traditional surgical approaches such as microfracture. Based on the findings, the company claimed that irrespective of a patient's age, HYALOFAST in combination with autologous adult mesenchymal stem cells (MSCs), can be successfully used as a treatment option for cartilage lesions.

With this breakthrough, we expect the market adoption of HYALOFAST to increase significantly, boosting Anika Therapeutics' sales performance. Notably, HYALOFAST is commercially available in more than 15 countries worldwide and has been used in more than 11,000 patients so far. Also, this trial result should advance the company's procedure of regulatory submission of HYALOFAST in the US. Under 'FastTRACK' Phase III trial, it is currently enrolling patients across the U.S. and Europe.

Demand for therapeutics-based treatment in the field of integrated orthopedics medicines and traumatic conditions, is growing in leaps and bounds these days. Per a recent report by Market Research Engine in this regard, global Orthopedic Devices Market will witness a CAGR of 5% from 2016 to 2022 and is projected to reach $47.50 billion by 2022.

Some of the big names in the orthopedic device market with promising growth potential are Stryker Corporation SYK , Smith & Nephew plc SNN and Orthofix International N.V. OFIX .

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Unexpected fountain of youth found in cardiac stem cells …

By JoanneRUSSELL25

Cardiac stem cells derived from young hearts helped reverse the signs of aging when directly injected into the old hearts of elderly rats, astudypublished Monday in the European Heart Journal demonstrated.

The old rats appeared newly invigorated after receiving their injections. As hoped, the cardiac stem cells improved heart function yet also provided additional benefits. The rats fur fur, shaved for surgery, grew back more quickly than expected, and their chromosomal telomeres, which commonly shrink with age, lengthened.

The old rats receiving the cardiac stem cells also had increased stamina overall, exercising more than before the infusion.

Its extremely exciting, said Dr. Eduardo Marbn, primary investigator on the research and director of the Cedars-Sinai Heart Institute. Witnessing the systemic rejuvenating effects, he said, its kind of like an unexpected fountain of youth.

Weve been studying new forms of cell therapy for the heart for some 12 years now, Marbn said.

Some of this research has focused on cardiosphere-derived cells.

Theyre progenitor cells from the heart itself, Marbn said. Progenitor cells are generated from stem cells and share some, but not all, of the same properties. For instance, they can differentiate into more than one kind of cell like stem cells, but unlike stem cells, progenitor cells cannot divide and reproduce indefinitely.

From hisown previous research, Marbn discovered that cardiosphere-derived cells promote the healing of the heart after a condition known as heart failure with preserved ejection fraction, which affects more than 50% of all heart failure patients.

Since heart failure with preserved ejection fraction is similar to aging, Marbn decided to experiment on old rats, ones that suffered from a type of heart problem thats very typical of what we find in older human beings: The hearts stiff, and it doesnt relax right, and it causes fluid to back up some, Marbn explained.

He and his team injected cardiosphere-derived cells from newborn rats into the hearts of 22-month-old rats thats elderly for a rat. Similar old rats received a placebo injection of saline solution. Then, Marbn and his team compared both groups to young rats that were 4 months old. After a month, they compared the rats again.

Even though the cells were injected into the heart, their effects were noticeable throughout the body, Marbn said

The animals could exercise further than they could before by about 20%, and one of the most striking things, especially for me (because Im kind of losing my hair) the animals regrew their fur a lot better after theyd gotten cells compared with the placebo rats, Marbn said.

The rats that received cardiosphere-derived cells also experienced improved heart function and showed longer heart cell telomeres.

The working hypothesis is that the cells secrete exosomes, tiny vesicles that contain a lot of nucleic acids, things like RNA, that can change patterns of the way the tissue responds to injury and the way genes are expressed in the tissue, Marbn said.

It is the exosomes that act on the heart and make it better as well as mediating long-distance effects on exercise capacity and hair regrowth, he explained.

Looking to the future, Marbn said hes begun to explore delivering the cardiac stem cells intravenously in a simple infusion instead of injecting them directly into the heart, which would be a complex procedure for a human patient and seeing whether the same beneficial effects occur.

Dr. Gary Gerstenblith, a professor of medicine in the cardiology division of Johns Hopkins Medicine, said the new study is very comprehensive.

Striking benefits are demonstrated not only from a cardiac perspective but across multiple organ systems, said Gerstenblith, who did not contribute to the new research. The results suggest that stem cell therapies should be studied as an additional therapeutic option in the treatment of cardiac and other diseases common in the elderly.

Todd Herron, director of the University of Michigan Frankel Cardiovascular Centers Cardiovascular Regeneration Core Laboratory, said Marbn, with his previous work with cardiac stem cells, has led the field in this area.

The novelty of this bit of work is, they started to look at more precise molecular mechanisms to explain the phenomenon theyve seen in the past, said Herron, who played no role in the new research.

One strength of the approach here is that the researchers have taken cells from the organ that they want to rejuvenate, so that makes it likely that the cells stay there in that tissue, Herron said.

He believes that more extensive study, beginning with larger animals and including long-term followup, is needed before this technique could be used in humans.

We need to make sure theres no harm being done, Herron said, adding that extending the lifetime and improving quality of life amounts to a tradeoff between the potential risk and the potential good that can be done.

Capicor, the company that grows these special cells, is focused solely on therapies for muscular dystrophy and heart failure with ongoing clinical trials involving human patients, Marbn said.

Capicor hasnt announced any plans to do studies in aging, but the possibility exists.

After all, the cells have been proven completely safe in over 100 human patients, so it would be possible to fast-track them into the clinic, Marbn explained: I cant tell you that there are any plans to do that, but it could easily be done from a safety viewpoint.

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‘Unexpected fountain of youth’ found in cardiac stem cells, says researcher – fox6now.com

By Sykes24Tracey

Cardiac stem cells derived from young hearts helped reverse the signs of aging when directly injected into the old hearts of elderly rats, astudypublished Monday in the European Heart Journal demonstrated.

The old rats appeared newly invigorated after receiving their injections. As hoped, the cardiac stem cells improved heart function yet also provided additional benefits. The rats fur, shaved for surgery, grew back more quickly than expected, and their chromosomal telomeres, which commonly shrink with age, lengthened.

The old rats receiving the cardiac stem cells also had increased stamina overall, exercising more than before the infusion.

Its extremely exciting, said Dr. Eduardo Marbn, primary investigator on the research and director of the Cedars-Sinai Heart Institute. Witnessing the systemic rejuvenating effects, he said, its kind of like an unexpected fountain of youth.

Weve been studying new forms of cell therapy for the heart for some 12 years now, Marbn said.

Some of this research has focused on cardiosphere-derived cells.

Theyre progenitor cells from the heart itself, Marbn said. Progenitor cells are generated from stem cells and share some, but not all, of the same properties. For instance, they can differentiate into more than one kind of cell like stem cells, but unlike stem cells, progenitor cells cannot divide and reproduce indefinitely.

From hisown previous research, Marbn discovered that cardiosphere-derived cells promote the healing of the heart after a condition known as heart failure with preserved ejection fraction, which affects more than 50% of all heart failure patients.

Since heart failure with preserved ejection fraction is similar to aging, Marbn decided to experiment on old rats, ones that suffered from a type of heart problem thats very typical of what we find in older human beings: The hearts stiff, and it doesnt relax right, and it causes fluid to back up some, Marbn explained.

He and his team injected cardiosphere-derived cells from newborn rats into the hearts of 22-month-old rats thats elderly for a rat. Similar old rats received a placebo injection of saline solution. Then, Marbn and his team compared both groups to young rats that were 4 months old. After a month, they compared the rats again.

Even though the cells were injected into the heart, their effects were noticeable throughout the body, Marbn said

The animals could exercise further than they could before by about 20%, and one of the most striking things, especially for me (because Im kind of losing my hair) the animals regrew their fur a lot better after theyd gotten cells compared with the placebo rats, Marbn said.

The rats that received cardiosphere-derived cells also experienced improved heart function and showed longer heart cell telomeres.

The working hypothesis is that the cells secrete exosomes, tiny vesicles that contain a lot of nucleic acids, things like RNA, that can change patterns of the way the tissue responds to injury and the way genes are expressed in the tissue, Marbn said.

It is the exosomes that act on the heart and make it better as well as mediating long-distance effects on exercise capacity and hair regrowth, he explained.

Looking to the future, Marbn said hes begun to explore delivering the cardiac stem cells intravenously in a simple infusion instead of injecting them directly into the heart, which would be a complex procedure for a human patient and seeing whether the same beneficial effects occur.

Dr. Gary Gerstenblith, a professor of medicine in the cardiology division of Johns Hopkins Medicine, said the new study is very comprehensive.

Striking benefits are demonstrated not only from a cardiac perspective but across multiple organ systems, said Gerstenblith, who did not contribute to the new research. The results suggest that stem cell therapies should be studied as an additional therapeutic option in the treatment of cardiac and other diseases common in the elderly.

Todd Herron, director of the University of Michigan Frankel Cardiovascular Centers Cardiovascular Regeneration Core Laboratory, said Marbn, with his previous work with cardiac stem cells, has led the field in this area.

The novelty of this bit of work is, they started to look at more precise molecular mechanisms to explain the phenomenon theyve seen in the past, said Herron, who played no role in the new research.

One strength of the approach here is that the researchers have taken cells from the organ that they want to rejuvenate, so that makes it likely that the cells stay there in that tissue, Herron said.

He believes that more extensive study, beginning with larger animals and including long-term followup, is needed before this technique could be used in humans.

We need to make sure theres no harm being done, Herron said, adding that extending the lifetime and improving quality of life amounts to a tradeoff between the potential risk and the potential good that can be done.

Capicor, the company that grows these special cells, is focused solely on therapies for muscular dystrophy and heart failure with ongoing clinical trials involving human patients, Marbn said.

Capicor hasnt announced any plans to do studies in aging, but the possibility exists.

After all, the cells have been proven completely safe in over 100 human patients, so it would be possible to fast-track them into the clinic, Marbn explained: I cant tell you that there are any plans to do that, but it could easily be done from a safety viewpoint.

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Scientists discovered how to rejuvenate rats by injecting stem cells into their hearts – Pulse Headlines

By Dr. Matthew Watson

On Monday, a group of scientists at Cedars-Sinai Heart Institute in Los Angeles, CA, discovered througha world-first experimenta form to rejuvenate elder rats old hearts by injecting cardiac stem cells from much younger rats with healthier hearts. They hope this process might eventually become useful to humans.

The first time an experiment like this was carried out was in 2009 by the same Los Angeles-based team. Now, they also proved the possibility of reversing aging in old hearts.

Heart failure is a typical cause of death in humans. Around 48 percent of women and 46 percent of men die a year from heart attacks and other heart-related diseases. They are the first reason of death worldwide, and a leading cause of death in the United States, killing over 375,000 Americans a year. Nearly half of all African-American population suffers from heart diseases.

Researchers took stem cells from the hearts of 4-month-old rats, shaped them into cardiosphere-derived cells and injected them into the hearts of other rats of 22 monthsold, an age that makes them be considered as old. They carried out a similar process to another group of rats but injected saline instead. Scientists later compared both groups.

After receiving the stem cells injection, researchers noted a significant change in the way old rats continued to live. They turned much more active and improved their functionalities. Not just their heart rates got better and faster, but also the way they ran and breathed. Their hair started to grow faster, their chromosomal telomeres which commonly shrink with age lengthened, plus other benefits. The rodents began to progressively improve their capacity of exercise along with their stamina overall.

The animals could exercise further than they could before by about 20%, and one of the most striking things, especially for me (because Im kind of losing my hair) the animals regrew their fur a lot better after theyd gotten cells compared with the placebo rats, said Dr Eduardo Marbn, director of the Cedars-Sinai Heart Institute and lead author, who is also extremely excited for having witnessed the unexpected fountain of youth.

In 2009, his team successfully repaired the damaged heart of a man who had suffered a heart attack, using his own heart tissue.

Stem cells are a really basic type of cells that can be molded and converted into other much-specialized cells through a process called differentiation, which is basicallyshaping them into any kind of body cell.They form in embryos like embryonic stem cells -, which help in the growth process of babies, along with the millions of other different cell types they need before their birth.

One of many cells scientists generated from stem cells is called progenitor cell, which shares some of the same properties. But unlike the original cells, progenitor cells are not able to divide and reproduce indefinitely. Dr. Marbn also said they discovered cardiosphere-derived cells, which tend to promote the healing of a condition that affects more than 50 percent of patients suffering from heart failure.

Our previous lab studies and human clinical trials have shown promise in treating heart failure using cardiac stem cell infusions, said Dr Marbn. Now we find that these specialized stem cells could turn out to reverse problems associated with aging of the heart.

According to Dr. Marbn, stem cells secrete exosomes, tiny vesicles which contain a lot of nucleic acids, things like RNA, that can change patterns of the way the tissue responds to injuries, and the way genes are expressed in the tissue. They are placed into the heart, and act to transform it into a better organ, helping it at the same time to improve exercise capacity and hair regrowth, he explained.

Now, Dr. Marbn is exploring a much easier way to deliver the stem cells intravenously, instead of injecting them directly into the heart. Thus avoiding surgeries, which tend to be more complicated and expensive for the patient.

Striking benefits are demonstrated not only from a cardiac perspective but across multiple organ systems, said Dr. Gary Gerstenblith, a professor of medicine in the cardiology division of Johns Hopkins Medicine, who did not contribute to the new research. The results suggest that stem cell therapies should be studied as an additional therapeutic option in the treatment of cardiac and other diseases common in the elderly.

Now, scientistsneed to make more extensive studies before using the technique in humans.

Source: CNN

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We Just Figured out How to Activate Stem Cells to Treat Baldness – Futurism

By raymumme

In BriefResearchers from UCLA have found a way to successfully reactivate stem cells in dormant hair follicles to promote hair growth in mice. Through this research, they've developed two drugs that could help millions of people worldwide treat conditions that lead to abnormal hair growth and retention.

Researchers have already explored ways to use stem cells totreat everything from diabetes toaging, and now, ateam from UCLAthinks they could potentially offer some relief for people suffering from baldness.

During their study, which has beenpublished in Nature, the researchers noticedthat stem cells found in hair follicles undergo a different metabolic process than normal skin cells. After turning glucose into a molecule known as pyruvate, these hair follicle cells then do one of two things: send the pyruvateto the cells mitochondria to be used as energy or convert it into another metabolite known as lactate.

Based on these findings, the researchers decided to see if inactive hair follicles behaved differently depending on the path of the pyruvate.

To that end, the UCLA team compared mice that had been genetically engineered so that they wouldnt produce lactate with mice that had been engineered to produce more lactate than normal. Obstructing lactate production stopped the stem cells in the follicles from being activated, while more hair growth was observed on the animals who were producing more of the metabolite.

No one knew that increasing or decreasing the lactate would have an effect on hair follicle stem cells, co-lead on the study and professor of molecular, cell, and developmental biology William Lowry explained in a UCLA press release. Once we saw how altering lactate production in the mice influenced hair growth, it led us to look for potential drugs that could be applied to the skin and have the same effect.

Based on their study, the researchers were able to discovertwo different drugs that could potentially help humans jumpstart the stem cells in their hair follicles to increase lactate production.

The first is called RCGD423, and it works by establishing a JAK/STAT signalling pathway between the exterior of a cell and its nucleus. This puts the stems cells in an active state and contributes to lactate production, encouraging hair growth.

The other drug, UK5099, takes the opposite approach. It stops pyruvate from being converted into energy by the cells mitochondria, which leaves the molecules with no choice but to take the alternate path of creating lactate, which, in turn, promotes hair growth.

Both of the drugs have yet to be tested on humans, but hopes are high that if tests are successful, they could provide relief for the estimated 56 million people in the U.S. alonesuffering from a range of conditions that affect normal hair growth and retention, including alopecia, hormone imbalances, stress-related hair loss, and even old age.

However, as undoubtedly pleased as many of those people would be to stimulate their hair growth, the potential relevance of this research stretches far beyond hair loss. The new knowledge gained regarding stem cells, specifically their relation to the metabolism of the human body, provides a very promising basis for future study in other realms.

I think weve only just begun to understand the critical role metabolism plays in hair growth and stem cells in general, noted Aimee Flores, first author of the study and a predoctoral trainee in Lowrys lab. Im looking forward to the potential application of these new findings for hair loss and beyond.

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Genome architecture guides stem cell fate, Stanford researchers find – Scope (blog)

By daniellenierenberg

When the sequence of the human genome was published in 2001 it was hailed as a great achievement. But now we know our genomes are much more (and much more mysterious) than a simple linear sequence of nucleotide letters. It coils around and over itself in ways that seem mindbogglingly complex. But recently researchers have begun to unravel this mystery and realize that dynamic changes in the genomes three-dimensional structure affect how and when important genes are expressed.

Now dermatologist Paul Khavari, MD, PhD, and graduate student Adam Rubin, former graduate student Brook Barajas, PhD, and researcher Mayra Furlan-Magaril, PhD, have used new mapping techniques to peer into the deepest recesses of tissue-specific stem cells progenitor cells that hang out in specialized tissues like muscle waiting for the call to divide and specialize. They identified two types of DNA contacts that help these cells answer a call to action. They published their resultsin Nature Genetics.

As Khavari explained to me in an email:

How the human genome rearranges itself to express genes needed for specific processes, such as stem cell differentiation, has been a mystery. This work shows that this not only involves physically changing DNA contacts, but also functionally activating contacts between pieces of DNA that were already established.It revises our understanding of the genome to a more living, breathing, moving entity that literally reconfigures itself as it changes its expression rather than a static template that is merely copied.

Specifically, Khavari and his colleagues found that the transformation from a tissue-specific stem cell into a more specialized cell (a process called differentiation) involves a two-step process: First the genomes of stem cells are prepped through a looping process that brings functional parts of the genome into close contact. Then the cells bide their time until the moment of differentiation, when proteins called transcription factors are unleashed to bind to these new DNA neighbors and stimulate the expression of genes necessary to launch the coming transformation.

As Khavari said:

This research illuminates a fundamental mechanism of genome regulation that has not been appreciated before. Specifically, a stem cell is pre-wired with established contacts to express a specific set of differentiation genes but only activates them when the dynamic loops are engaged. By analogy with a race, the runners are all at the starting line and ready to run in that particular event but only the firing of the gun sets the specific event in motion.

This pre-wiring not only allows the stem cells to respond quickly to differentiation signals, but it also locks them into a specific fate, the researchers believe. In this way, a muscle stem cell avoids any missteps that could result in it mistakenly becoming a skin or a blood cell rather than a muscle cell. Interestingly, the researchers also found clues suggesting that perturbations in this looping process are sometimes associated with the development of certain diseases, including skin cancer and psoriasis.

Previously: Inducible loops enable 3D gene expression studies, The quest to unravel complex DNA structures gets a boost from new technology and NIH fundingand DNA origami: How our genomes foldPhoto by Braden Collum

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A Low-Calorie Diet Slows Aging – Anti Aging News

By LizaAVILA

New research reveals that a low-calorie diet rejuvenates the biological clock in a powerful manner, keeping the body younger.

Scientists have determined that a diet low in calories facilitates the energy-regulating processes. A low-calorie diet also helps to keep the body younger. These results were recently outlined in Cell. The finding is attributable to scientists at the University of California at Irvine's Center for Epigenetics and Metabolism. The team of scientists has revealed the manner in which the body's circadian rhythms alter due to the aging process. These rhythms are the body's biological clock. The circuit controlled by the clock directly connectedto aging is centered on the efficient metabolism of energy in cells.

About the Study

The group of scientists used mice for their study. These mice were tested at six months and at 18 months of age. Tissue samples were taken from their livers. This isthe organ that serves as the interface between food intake and energy distribution within the body. Energy is metabolized in cells in accordance with nuanced circadian controls.

Findings

The scientists determined the 24-hour cycle of the older mice's metabolic systems stayed the same. There were significant changes in the circadian mechanism that triggers genes on and off according to the usage of energy within cells. This means older cells process energy in an inefficient manner. The mechanism works quite well in young mice but shuts off in older mice.

A second group of older mice was provided with a diet containing 30 percent fewer calories. This intake period lasted half a year. Energy processing in the cells ended up more than unchanged. Caloric restriction functions through a rejuvenation of the biological clock. Inthe context of the study, good aging is the result of a good clock.

Collaboration for Confirmation

A companion study outlined in Cell explains the work performed by a group of researchers from the Barcelona Institute for Research in Biomedicine. These researchers collaborated with the team described above to gauge body clock functionality in stem cells from the muscle and skin of young and old mice. They determined a diet low in calories conserved the majority of rhythmic functions that occur during youth. This is the additional proof needed to show a low-calorie diet significantly contributes to the prevention of the aging process's effects. It is important to keep the stem cells' rhythm young as these cells will function to renew and preserve day-night tissue cycles.

Consuming less food seems to ward off tissue aging. As a result, stem cells do notreprogram circadian activities. Thestudies described above are important as they help explain why low-calorie diets slow aging in mice. The same results might hold true for human beings.

The Study's Importance

Prior fruit fly studies have shown diets low in calories boost longevity. However, the research described above is the first to show caloric restriction impacts circadian rhythms' impact on cell aging. These studies reveal the cell path through which the aging process is controlled. The findings serve as an introduction as to how the elements of aging can be controlled in terms of pharmacology.

What's Next?

The scientists involved in these studies are adamant it is necessary to continue examining why metabolism produces a dominant effect on stem cell aging. When the link that delays or promotes aging has been pinpointed, treatments must be developed to regulate the link.

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Stem cell therapy may yield positive results for worn-out knees – Waterloo Cedar Falls Courier

By Dr. Matthew Watson

Dear Doctor: I read you can use your own stem cells to rejuvenate worn-out knees. Does this really work?

Dear Reader: Worn out is a good way to term what happens to the knee joint with prolonged use. Lets look at how this happens, starting with cartilage.

The lower portion of the knee joint (at the tibia) contains shock absorbers called menisci made of cartilage. You have one on the inner portion and another on the outer portion of each knee. The upper portion of the knee joint (at the femur) is lined with cartilage as well. All of this cartilage helps protect the bones at the joint but it doesnt heal or regenerate well due to limited blood supply. When severe, worn cartilage leads to arthritis of the knee. In knee X-rays of people older than 60, 37 percent have shown evidence of arthritis of the knees.

The intriguing thing about stem cells is they have the ability to become any type of cell the body needs. The cells used for stem cell injections in the knees are called mesenchymal stem cells, and they can differentiate into bone, fat or cartilage cells. These stem cells can come from the fat cells of your body, from your bone marrow or from the inner lining of your knee joint; theyre then replicated in the laboratory and injected into the knee joint.

In a 2014 study, 55 patients who had surgery for meniscal tears of the knees were separated into three groups, with two of the groups receiving stem cell injections. Researchers found, after six weeks, pain had decreased substantially in the two groups that received stem cell injections and the decrease was even greater at one and two years after the injection.

In a 2017 study in the British Journal of Sports Medicine, researchers analyzed six studies that used stem cells for osteoarthritis of the knees. In five of the studies, stem cells were given after surgery to the knee; in the other study, stem cells from a donor were administered without surgery. All the studies showed reduced pain and improved knee function. Further, in three of the four trials, MRIs corroborated the cartilage improvements. However, the authors noted, five of the six studies were of such poor methodology that an overall conclusion about the stem cells effectiveness could not be made.

In all these studies, the most common side effect was knee swelling and stiffness, which improved over time.

There may be benefit to stem cell injections for cartilage loss of the knees, but more data is needed, especially in those who arent having surgery of the knee. Id also like to see more data on this type of therapy as a preventive measure for younger patients before their knees are worn out.

Send questions to askthedoctors@mednet.ucla.edu, or write: Ask the Doctors, c/o Media Relations, UCLA Health, 924 Westwood Blvd., Suite 350, Los Angeles, CA, 90095.

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Twins’ Bartolo Coln: ‘The older I get, the more I want to play.’ – Winona Daily News

By JoanneRUSSELL25

DETROIT Near the open doorway in the Comerica Park visitors clubhouse is a sign warning the curious to stay out of the kitchen. No media, it reads, making its point in all caps. So, its with some irony that a few feet away, Bartolo Coln agrees to a brief one-on-one with a reporter, his first since joining the Minnesota Twins.

Coln has fulfilled his media requirements when he starts, speaking with reporters through Twins interpreter Carlos Font about his performances, but thats where he prefers to leave it. Hes easy to find in the clubhouse, and will say hello and shake your hand, but he also makes it clear that its not going any further which would be fine if he hadnt become an essential part of the Twins playoff chase.

When the Twins signed Coln to a minor league deal on July 7, the primary response was laughter. This is the help the American League Centrals surprise team is getting for the stretch run, a 44-year-old with a 2-8 record and 8.14 earned-run average who had just been given his outright release by the Atlanta Braves?

Well, no ones laughing now.

I think it probably raised a few eyebrows when we brought him in, but hes been valuable, manager Paul Molitor said.

What appears to be happening is another in a string of career resurrections for the right-hander who broke in with the Cleveland Indians in 1997, won a Cy Young Award in 2005 and signed his first free-agent minor league deal with Boston in 2008. Hes no longer throwing hard, but his control remains as sharp as his competitive nature.

The older I get, the more I want to play, he said.

Over his past three starts, Coln is 2-0 with a 2.82 ERA with three walks and 11 strikeouts in 22.1 innings pitched. In his last start, he became the oldest AL pitcher to throw a complete game since Hall of Famer Nolan Ryan did it for Texas in 1992. On Tuesday, hell make the most important start of the season so far in the opener of a three-game series against the first-place Cleveland Indians at Target Field.

That explains the persistence that has kept alive a career that has seemed dead more than once. It was a whopping nine years ago that Coln first signed a minor league deal with a spring training invite, a cheap gambit by the Boston Red Sox. In four seasons from 2006-09, he went 14-21 with a 5.18 ERA with three clubs while batting elbow and shoulder problems. He missed all of 2010.

I thought I was going to be done, he said.

Coln credits 2010 stem-cell treatment fat and bone marrow was re-injected into his elbow and shoulder for saving his arm. Major League Baseball studied the treatment to see if it fell under its performance-enhancing drug policy, but it has since become a popular, if not quite trumpeted, treatment for pitchers hoping to avoid reconstructive surgery.

It has helped me to keep my arm young and keep me going, Coln said.

Coln, however, did fall afoul of MLB when he tested positive for testosterone in August 2012. He was 39, and many suspected had finally hit the end of the road. Yet, he returned the next season with Oakland and went 18-6 with a 2.65 ERA and an AL-best three shutouts.

Last season, he went 15-8 with a 3.34 ERA with the Mets, parlaying the season into a one-year, $12.5 million deal with Atlanta. The Braves are still on the hook for most of that contract, meaning the Twins are getting Coln at a bargain, prorated league minimum roughly $220,000.

He chose the Twins over the Mets after receiving a call from friend and former teammate in Anaheim, Ervin Santana.

The Mets and the Twins were the teams requesting my services, and I was weighing my options, Coln said. Ervin Santana called me and asked me to come and told me how good the organization was, how good the team was. After I started looking at it, and seeing how young their pitching was and how many young kids we had on the team, and I thought its not only an opportunity for me to pitch, but an opportunity to teach other young players how to pitch and how to be big-leaguers.

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Does recovery occur after spinal cord injury? | Answers …

By NEVAGiles23

Many doctors tell patients and families that recovery does not occur after spinal cord injury. This is not true. Recovery is the rule, not the exception after spinal cord injury.

Segmental recovery. Most patients recover 1-2 segments below the injury site, even after so-called complete spinal cord injuries. For example, a person with a C4/5 injury may have deltoid function on admission and then recover biceps (C5), wrist extensors (C6), and perhaps even triceps (C7) after several months, and the associated dermatomes.

Recovery due to methylprednisolone. The second National Acute Spinal Cord Injury Study (NASCIS 2) showed that patients with complete spinal cord injuries and who did not receive the high-dose steroid methylprednisolone recovered on average 8% of motor function they had lost. If they received methylprednisolone within 8 hours after injury, they recovered on average 21% of what they had lost. In contrast, people with incomplete spinal cord injury recovered on average 59% of motor function and 75% if treated with high dose methylprednisolone.

Recovery of postural reflexes. Most people with cervical or upper thoracic spinal cord injury are initially unable to control their trunk muscles. However, most will recover better trunk control over months or even years after injury.

Walking quads and paras. Most people with incomplete spinal cord injuries, i.e. ASIA C, will recover standing or walking. Walking recovery after complete spinal cord injuries, i.e. ASIA A, are rare but can occur in 5% of the cases. In the 1980s, less than 40% of spinal cord injuries admitted to hospital were incomplete. However, in the 1990s, over 60% of spinal cord injuries are incomplete and thus the incidence of walking quads or walking paras may be higher than most people think.

Both animal and human studies indicate that as little as 10% of spinal cord tracts can support substantial function, including locomotion. People often can walk even though a tumor has damaged 90% of their spinal cord. This is due to the redundancy and plasticity of the spinal cord. Multiple spinal pathways serve similar or overlapping functions. Plasticity refers to the ability of axons to sprout and make new connections. Because transected spinal cords are rare, most people have some spinal axons crossing the injury site. This is the basis of the hope that even slight regeneration of the spinal cord will restore substantial function.

Experimental Therapies for Subacute Spinal Cord Injury

Several experimental therapies are being tested in clinical trial for spinal cord injury during the first days or weeks after injury.

Monosialic ganglioside (GM1, Sygen). In 1991, Fred Geisler and colleagues reported that GM1 injected daily for 6 weeks after injury improve locomotor recovery 37 patients. Fidia Pharmaceutical subsequently tested this therapy in a large multicenter clinical trial in 800 patients, showing that the GM1 accelerated recovery during the first six weeks but did not significantly improve the extent of recovery at 6-12 months after injury. Note that this trial is no longer active. Although the drug is still available in Europe and South America, the company Fidia has been bought by another company. CareCure Forum (GM1) Link

Activated macrophage transplants. In 1998, Michal Schwartz at the Weizmann Institute reported that activated macrophages obtained from blood and transplanted to the spinal cord improve functional recovery in rats. The company Proneuron initiated phase 1 clinical trials to assess feasibility and safety of macrophage transplants in human spinal cord injury. Preliminary reports suggest that the treatment is feasible and safe. All the patients had complete thoracic spinal cord injury and received macrophage transplants within 2 weeks after injury. Three of the 8 patients recovered from ASIA A to ASIA C, more than the expected 5%. A phase 1 clinical trial is continuing at Erasmus Hospital in Brussels, Belgium. A phase 2 trial is being planned in two U.S. centers including Craig Hospital in Denver (CO) and Mt. Sinai in New York City (NY). CareCure Forum (Macrophage) Link

Alternating Current Electrical Stimulation. In 1999, Richard Borgens and colleagues at Purdue University reported that alternating currents applied to dog spinal cords stimulated regeneration and recovery of function in dogs with spinal cord injury. A clinical trial has commenced at Purdue University for people who are within 2 weeks after acute spinal cord injury. CareCure Forum (AC Stim) Link

AIT-082 (Neotrofin). This is a guanosine analog that can be taken orally and reportedly increases neurotrophins or neural growth factors in the brain and spinal cord. Neotherapeutics tested this drug in patients with Alzheimers disease. They started a multicenter clinical trial at Ranchos Los Amigos in Downey (CA), Gaylord Hospital in Wallingford (CT), and Thomas Jefferson Hospital in Philadelphia. The treatment must be started within 2 weeks after spinal cord injury. CareCure Forum (AIT-082) Link

Experimental Therapies for Chronic Spinal Cord Injury

Several therapies are being tested in clinical trials for chronic spinal cord injury, i.e. people whose neurological recovery has stabilized one or more years after injury. Many other treatments are being considered for clinical trial (see article on Advances in Spinal Cord Injury Therapy 25 November 2002).

4-aminopyridine (4-AP). This drug is a small molecule that blocks fast voltage sensitive potassium channel blockers. The drug can be obtained by physician prescription from compounding pharmacies in the United States. In addition, Acorda Therapeutics is carrying out a multicenter phase 3 clinical trial of a sustained release formulation of the drug in people who are more than one and a half years after incomplete spinal cord injury. The drug may improve conduction of demyelinated axons in the spinal cord and preliminary clinical trial results suggest that the drug may reduce spasticity and improve motor or sensory function in as many as a third of people with chronic spinal cord injury. See CareCure Forum (4-AP) Link

Fetal porcine stem cell transplants. Embryonic stem cells have attracted much attention. Several studies of human fetal cell transplants have been carried out in Sweden, Russia, and the United States, showing that transplanted fetal cells will engraft in human spinal cords. However, due in part of the lack of availability of adult human stem cells for transplantation and politics associated with the use of embryonic human stem cells, the first and only stem cell therapy trial for spinal cord injury in the United States used fetal stem cells from pigs. A phase 1 clinical trial at Washington University in St. Louis (MO) and Albany Medical Center in Albany (NY) has transplanted fetal stem obtained from pig fetuses and treated with antibodies to reduce the immune rejection. Sponsored by Diacrin, this trial is aiming to test 10 patients. See CareCure Forum (Diacrin) Link

Olfactory ensheathing glial transplants. Olfactory ensheathing glia (OEG) reside in the olfactory nerve and the olfactory bulb. They are believed to be why the olfactory nerve continuously regenerates in adults. OEG cells are made in the nasal mucosa and migrate up the nerve to the olfactory bulb. Several laboratories have shown that OEG transplants facilitate regeneration of the spinal cord. Three clinical trials have started in Lisbon (Portugal), Brisbane (Australia), and Beijing (China). In Lisbon, they are transplanting nasal mucosa obtained from the patient into the spinal cord. In Brisbane, they are culturing OEG cells from nasal mucosa and transplanting the cells to the spinal cord. In Beijing, they are culturing OEG from human fetal olfactory bulbs and transplanting into the spinal cord. See CareCure Forum Link (Brisbane) and CareCure Forum Link (Beijing)

Summary

Spinal cord injury is devastating, not only for the injured person but for families and friends. While much information is available on Internet, most of the material is scattered and out of date. This article summarizes answers to some of the most frequently asked questions by people who are encountering spinal cord injury for the first time. Spinal cord injury disconnects the brain from the body. This leads not only to loss of sensation and motor control below the injury site but may be associated with abnormal activities of the spinal cord both above and below the injury site, resulting in spasticity, neuropathic pain, and autonomic dysreflexia. Many functions of our body that we take for granted, such as going to the bathroom, sexual function, blood pressure and heart rate, digestion, temperature control and sweating, and other autonomic functions may not only be lost but may be abnormally active. Finally, contrary to popular notions about spinal cord injury, recovery is the rule and not the exception in spinal cord injury. The recovery takes a long time and may be slowed down or blocked by the muscle atrophy and learned non-use. Finally, there is hope. Many therapies have been shown to regenerate and remyelinate the spinal cord. Some of these are now in clinical trials and many more should be in clinical trial soon.

Recovery and TreatmentWise Young, MD, PhD

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Asterias Announces Major AST-VAC2 Development Milestone: First … – GlobeNewswire (press release)

By NEVAGiles23

FREMONT, Calif., Aug. 14, 2017 (GLOBE NEWSWIRE) -- Asterias Biotherapeutics, Inc. (NYSE MKT:AST), a biotechnology company pioneering the field of regenerative medicine, today announced that Cancer Research UK, supported by Asterias technical personnel, has successfully completed manufacture of the first cGMP (current Good Manufacturing Practice) clinical grade lot of AST-VAC2, which meets all specifications for release. This lot will provide clinical trial material for patients enrolling in the first clinical study evaluating AST-VAC2 in non-small cell lung cancer.

The successful production of this first cGMP lot of AST-VAC2 is a major step towards initiating the upcoming study in non-small cell lung cancer, said Mike Mulroy, President and Chief Executive Officer. With its potential as a ready-to-use, off-the-shelf cancer immunotherapy, AST-VAC2 represents an exciting opportunity for Asterias in the rapidly evolving cancer immunotherapy sector.

Investigational therapies intended for human clinical applications must be manufactured in accordance with cGMP standards designed to help assure the safety and potency of drug products. To achieve cGMP standards, a product must be manufactured and released according to rigorous systems designed to ensure appropriate control of manufacturing facilities, equipment, raw materials, processes and testing procedures. Under the companys agreement with Cancer Research UK, Asterias has transferred its innovative laboratory scale AST-VAC2 manufacturing process to Cancer Research UKs Biotherapeutics Development Unit, which has developed and optimized the process for cGMP manufacture and is responsible for producing cGMP AST-VAC2 for use in the upcoming clinical study in non-small cell lung cancer.

About AST-VAC2

AST-VAC2 is an innovative immunotherapy product that contains mature dendritic cells derived from pluripotent stem cells. These non-patient specific (allogeneic) AST-VAC2 cells are engineered to express a modified form of telomerase, a protein widely expressed in tumor cells, but rarely found in normal cells. The modified form of telomerase permits enhanced stimulation of immune responses to the protein. The AST-VAC2 dendritic cells instruct the immune system to generate responses against telomerase which will target tumor cells. AST-VAC2 is based on a specific mode of action that is complementary and potentially synergistic to other immune therapies.

About Non-Small Cell Lung Cancer

Lung cancer (both small cell and non-small cell) is the leading cause of cancer-related death, accounting for about one-quarter of all cancer deaths and more than colorectal, breast, and prostate cancers combined. Non-small cell lung cancer (NSCLC) accounts for about 80% to 85% of lung cancers, according to the American Cancer Society. The three main types of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. The American Cancer Societys estimates for lung cancer in the United States for 2017 are: about 222,500 new cases of lung cancer, and about 155,870 deaths from lung cancer. Despite the large number of people afflicted by non-small cell lung cancer, patients remain vastly underserved due to a scarcity of effective treatments. According to statistics published by Cancer Research UK, the five year survival rate for lung cancer patients in England and Wales is less than 10%.

About Asterias Biotherapeutics

Asterias Biotherapeutics, Inc. is a biotechnology company pioneering the field of regenerative medicine. The company's proprietary cell therapy programs are based on its pluripotent stem cell and immunotherapy platform technologies. Asterias is presently focused on advancing three clinical-stage programs which have the potential to address areas of very high unmet medical need in the fields of neurology and oncology. AST-OPC1 (oligodendrocyte progenitor cells) is currently in a Phase 1/2a dose escalation clinical trial in spinal cord injury. AST-VAC1 (antigen-presenting autologous dendritic cells) is undergoing continuing development by Asterias based on promising efficacy and safety data from a Phase 2 study in Acute Myeloid Leukemia (AML), with current efforts focused on streamlining and modernizing the manufacturing process. AST-VAC2 (antigen-presenting allogeneic dendritic cells) represents a second generation, allogeneic cancer immunotherapy. The company's research partner, Cancer Research UK, plans to begin the first clinical trial of AST-VAC2 in non-small cell lung cancer in 2017. Additional information about Asterias can be found at http://www.asteriasbiotherapeutics.com.

About Cancer Research UK

Cancer Research UK is the worlds leading cancer charity dedicated to saving lives through research. Cancer Research UKs pioneering work into the prevention, diagnosis and treatment of cancer has helped save millions of lives. Cancer Research UK receives no government funding for its life-saving research. Every step it makes towards beating cancer relies on vital donations from the public. Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.

FORWARD-LOOKING STATEMENTSStatements pertaining to future financial and/or operating and/or clinical research results, future growth in research, technology, clinical development, and potential opportunities for Asterias, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "anticipates," "expects," "estimates") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the businesses of Asterias, particularly those mentioned in the cautionary statements found in Asterias' filings with the Securities and Exchange Commission. Asterias disclaims any intent or obligation to update these forward-looking statements.

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Which research results in mice will help humans with MS? Now there’s a way to tell – UB News Center

By daniellenierenberg

BUFFALO, N.Y. People with multiple sclerosis (MS) knowall too well the frustration of hearing that success in treatingthe disease in mice had little or no effect in humans.

Unfortunately, with no large animal models for MS, results thatsuggest promising new treatments in mice often are ineffective inhumans.

Now, University at Buffalo researchers have developed andsuccessfully tested a method for determining how relevant to thehuman disease findings are from mouse models. The researchwas published Aug. 8 in Stem Cell Reports.

This is an important resource for the field as it allowsus to compare human and rodent cells, and provides a point ofreference to understand whether or not gene expression patterns areconserved between species, said Fraser Sim, PhD, seniorauthor and associate professor in the Department of Pharmacologyand Toxicology in the Jacobs School of Medicine and BiomedicalSciences at UB. Co-first authors are Suyog U. Pol PhD, now apostdoctoral fellow, and Jessie J. Polanco, a doctoral candidate,both in the medical school.

MS trial failures

There have been so many failures in clinical trials forMS when promising observations are translated from small animalmodels to the clinic, Sim said. Our primarymotivation was to try to understand, at a molecular level, how thehuman cells responsible for synthesizing myelin differ from theirmuch-better-studied mouse counterparts.

MS and some other neurological diseases occur when there isdamage to myelin the fatty sheath that allows nerve cellsto communicate. So the myelin-producing cells, called humanoligodendrocyte progenitor cells, or OPCs, found in the brain andspinal cord have been a major focus of efforts to better understandMS and develop potential new treatments for it.

Sim explained that undifferentiated OPCs are frequently found inthe brain lesions of MS patients, so boosting the differentiationof these cells could lead to myelination and a reduction ofsymptoms.

From OPCs to oligodendrocytes

One reason why so many clinical trials fail may be because offundamental differences in the types and levels of genes expressedbetween mice and humans. Sim and his colleagues addressed thisquestion by performing gene-expression analysis on differentiatinghuman OPCs.

In this paper, we describe the transcriptional eventsthat underlie how human OPCs develop into oligodendrocytes,said Sim.

To do it, they used a network analysis software tool calledweighted gene coexpression network analysis (WCGNA). The softwareclusters together genes with similar patterns of expression. Italso allows for analysis of both conserved and divergent geneexpression between humans and rodents.

WCGNA looks at the relationships between genes ratherthan absolute differences between conditions in any givenexperiment, Sim said.

He added that the information encoded in levels of geneexpression increasing or decreasing is very reliable andreproducible.

We performed WCGNA in exactly the same manner on cellsisolated from mice, rats and humans, and prepared these cells in asclose to matched conditions as possible, trying to keep things assimilar as possible to facilitate this comparison, saidSim.

It turned out several of the genes the team had identified asrelevant to human disease also are involved in mouse developmentand mouse models of myelin disease.

New myelin-repairing gene

Based on its findings from that analysis, the team had predictedthat GNB4, a protein involved in signal transduction, would beinvolved in the development of OPCs in humans. The researchersfound that over-production of GNB4, a protein involved in thetransduction of extracellular signals, could cause human OPCs torapidly undergo myelination when transplanted into a model forhuman cell therapy in MS.

So this proteins expression in oligodendrocyteprogenitor cells might ultimately become a therapeutic target,potentially promoting oligodendrocyte formation in MSpatients, said Sim.

The approach also identified several other important candidatesthat play key roles in regulating the development of humanoligodendrocytes.

Other co-authors on the paper are Melanie A. OBara,research scientist; Hani J. Shayya, a UB undergraduate and Karen C.Dietz, PhD, research assistant professor, all of the Department ofPharmacology and Toxicology and Richard A. Seidman, amasters candidate in neuroscience.

The research was funded by the National Multiple SclerosisSoociety, the Kalec Multiple Sclerosis Foundation, the SkarlowMemorial Trust and the Empire State Stem Cell Fund (NYSTEM) throughthe New York State Department of Health.

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UCLA Scientists Identify a New Way to Activate Stem Cells to Make Hair Grow – Newswise (press release)

By LizaAVILA

Mirabai Vogt-James

Newswise UCLA researchers have discovered a new way to activate the stem cells in the hair follicle to make hair grow. The research, led by scientists Heather Christofk and William Lowry, may lead to new drugs that could promote hair growth for people with baldness or alopecia, which is hair loss associated with such factors as hormonal imbalance, stress, aging or chemotherapy treatment.

The researchwas publishedin the journal Nature Cell Biology.

Hair follicle stem cells are long-lived cells in the hair follicle; they are present in the skin and produce hair throughout a persons lifetime. They are quiescent, meaning they are normally inactive, but they quickly activate during a new hair cycle, which is when new hair growth occurs. The quiescence of hair follicle stem cells is regulated by many factors. In certain cases they fail to activate, which is what causes hair loss.

In this study, Christofk and Lowry, ofEli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, found that hair follicle stem cell metabolism is different from other cells of the skin. Cellular metabolism involves the breakdown of the nutrients needed for cells to divide, make energy and respond to their environment. The process of metabolism uses enzymes that alter these nutrients to produce metabolites. As hair follicle stem cells consume the nutrient glucose a form of sugar from the bloodstream, they process the glucose to eventually produce a metabolite called pyruvate. The cells then can either send pyruvate to their mitochondria the part of the cell that creates energy or can convert pyruvate into another metabolite called lactate.

Our observations about hair follicle stem cell metabolism prompted us to examine whether genetically diminishing the entry of pyruvate into the mitochondria would force hair follicle stem cells to make more lactate, and if that would activate the cells and grow hair more quickly, said Christofk, an associate professor of biological chemistry and molecular and medical pharmacology.

The research team first blocked the production of lactate genetically in mice and showed that this prevented hair follicle stem cell activation. Conversely, in collaboration with the Rutter lab at University of Utah, they increased lactate production genetically in the mice and this accelerated hair follicle stem cell activation, increasing the hair cycle.

Before this, no one knew that increasing or decreasing the lactate would have an effect on hair follicle stem cells, said Lowry, a professor of molecular, cell and developmental biology. Once we saw how altering lactate production in the mice influenced hair growth, it led us to look for potential drugs that could be applied to the skin and have the same effect.

The team identified two drugs that, when applied to the skin of mice, influenced hair follicle stem cells in distinct ways to promote lactate production. The first drug, called RCGD423, activates a cellular signaling pathway called JAK-Stat, which transmits information from outside the cell to the nucleus of the cell. The research showed that JAK-Stat activation leads to the increased production of lactate and this in turn drives hair follicle stem cell activation and quicker hair growth. The other drug, called UK5099, blocks pyruvate from entering the mitochondria, which forces the production of lactate in the hair follicle stem cells and accelerates hair growth in mice.

Through this study, we gained a lot of interesting insight into new ways to activate stem cells, said Aimee Flores, a predoctoral trainee in Lowrys lab and first author of the study. The idea of using drugs to stimulate hair growth through hair follicle stem cells is very promising given how many millions of people, both men and women, deal with hair loss. I think weve only just begun to understand the critical role metabolism plays in hair growth and stem cells in general; Im looking forward to the potential application of these new findings for hair loss and beyond.

The use of RCGD423 to promote hair growth is covered by a provisional patent application filed by the UCLA Technology Development Group on behalf of UC Regents. The use of UK5099 to promote hair growth is covered by a separate provisional patent filed by the UCLA Technology Development Group on behalf of UC Regents, with Lowry and Christofk as inventors.

The experimental drugs described above were used in preclinical tests only and have not been tested in humans or approved by the Food and Drug Administration as safe and effective for use in humans.

The research was supported by the California Institute for Regenerative Medicine training grant, a New Idea Award from the Leukemia Lymphoma Society, the National Cancer Institute (R25T CA098010), the National Institute of General Medical Sciences (R01-GM081686 and R01-GM0866465), the National Institutes of Health (RO1GM094232), an American Cancer Society Research Scholar Grant (RSG-16-111-01-MPC), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (5R01AR57409), a Rose Hills Foundation Research Award and the Gaba Fund; the Rose Hills award and the Gaba Fund are administered through the UCLA Broad Stem Cell Research Center.

Further research on the use of UK5099 is being funded by the UCLA Technology Development Group through funds fromCalifornia State Assembly Bill 2664.

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