Stem cells hold keys to body's plan

PUBLIC RELEASE DATE:

5-Jun-2014

Contact: Jeannette Spalding jeannette.spalding@case.edu 216-368-3004 Case Western Reserve University

Cleveland June 5, 2014 Case Western Reserve researchers have discovered landmarks within pluripotent stem cells that guide how they develop to serve different purposes within the body. This breakthrough offers promise that scientists eventually will be able to direct stem cells in ways that prevent disease or repair damage from injury or illness. The study and its results appear in the June 5 edition of the journal Cell Stem Cell.

Pluripotent stem cells are so named because they can evolve into any of the cell types that exist within the body. Their immense potential captured the attention of two accomplished faculty with complementary areas of expertise.

We had a unique opportunity to bring together two interdisciplinary groups, said co-senior author Paul Tesar, PhD, Assistant Professor of Genetics and Genome Sciences at CWRU School of Medicine and the Dr. Donald and Ruth Weber Goodman Professor.

"We have exploited the Tesar labs expertise in stem cell biology and my labs expertise in genomics to uncover a new class of genetic switches, which we call seed enhancers, said co-senior author Peter Scacheri, PhD, Associate Professor of Genetics and Genome Sciences at CWRU School of Medicine. Seed enhancers give us new clues to how cells morph from one cell type to another during development."

The breakthrough came from studying two closely related stem cell types that represent the earliest phases of development embryonic stem cells and epiblast stem cells, first described in research by Tesar in 2007. These two stem cell types give us unprecedented access to the earliest stages of mammalian development, said Daniel Factor, graduate student in the Tesar lab and co-first author of the study.

Olivia Corradin, graduate student in the Scacheri lab and co-first author, agrees. Stem cells are touted for their promise to make replacement tissues for regenerative medicine, she said. But first, we have to understand precisely how these cells function to create diverse tissues.

Enhancers are sections of DNA that control the expression of nearby genes. By comparing these two closely related types of pluripotent stem cells (embryonic and epiblast), Corradin and Factor identified a new class of enhancers, which they refer to as seed enhancers. Unlike most enhancers, which are only active in specific times or places in the body, seed enhancers play roles from before birth to adulthood.

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Stem cells hold keys to body's plan

New Method Reveals Single Protein Interaction Key to Embryonic Stem Cell Differentiation

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Newswise Proteins are responsible for the vast majority of the cellular functions that shape life, but like guests at a crowded dinner party, they interact transiently and in complex networks, making it difficult to determine which specific interactions are most important.

Now, researchers from the University of Chicago have pioneered a new technique to simplify the study of protein networks and identify the importance of individual protein interactions. By designing synthetic proteins that can only interact with a pre-determined partner, and introducing them into cells, the team revealed a key interaction that regulates the ability of embryonic stem cells to change into other cell types. They describe their findings June 5 in Molecular Cell.

Our work suggests that the apparent complexity of protein networks is deceiving, and that a circuit involving a small number of proteins might control each cellular function, said senior author Shohei Koide, PhD, professor of biochemistry & molecular biophysics at the University of Chicago.

For a cell to perform biological functions and respond to the environment, proteins must interact with one another in immensely complex networks, which when diagrammed can resemble a subway map out of a nightmare. These networks have traditionally been studied by removing a protein of interest through genetic engineering and observing whether the removal destroys the function of interest or not. However, this does not provide information on the importance of specific protein-to-protein interactions.

To approach this challenge, Koide and his team pioneered a new technique that they dub directed network wiring. Studying mouse embryonic stem cells, they removed Grb2, a protein essential to the ability of the stem cell to transform into other cell types, from the cells. The researchers then designed synthetic versions of Grb2 that could only interact with one protein from a pool of dozens that normal Grb2 is known to network with. The team then introduced these synthetic proteins back into the cell to see which specific interactions would restore the stem cells transformative abilities.

The name, directed network wiring, comes from the fact that we create minimalist networks, Koide said. We first remove all communication lines associated with a protein of interest and add back a single line. It is analysis by addition.

Despite the complexity of the protein network associated with stem cell development, the team discovered that restoring only one interactionbetween Grb2 and a protein known as Ptpn11/Shp2 phosphatasewas enough to allow stem cells to again change into other cell types.

We were really surprised to find that consolidating many interactions down to a single particular connection for the protein was sufficient to support development of the cells to the next stage, which involves many complicated processes, Koide said. Our results show that signals travel discrete and simple routes in the cell.

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New Method Reveals Single Protein Interaction Key to Embryonic Stem Cell Differentiation

Fasting triggers stem cell regeneration of damaged, old immune system

PUBLIC RELEASE DATE:

5-Jun-2014

Contact: Suzanne Wu suzanne.wu@usc.edu 213-740-0252 University of Southern California

In the first evidence of a natural intervention triggering stem cell-based regeneration of an organ or system, a study in the June 5 issue of the Cell Press journal Cell Stem Cell shows that cycles of prolonged fasting not only protect against immune system damage a major side effect of chemotherapy but also induce immune system regeneration, shifting stem cells from a dormant state to a state of self-renewal.

In both mice and a Phase 1 human clinical trial, long periods of not eating significantly lowered white blood cell counts. In mice, fasting cycles then "flipped a regenerative switch": changing the signaling pathways for hematopoietic stem cells, which are responsible for the generation of blood and immune systems, the research showed.

The study has major implications for healthier aging, in which immune system decline contributes to increased susceptibility to disease as we age. By outlining how prolonged fasting cycles periods of no food for two to four days at a time over the course of six months kill older and damaged immune cells and generate new ones, the research also has implications for chemotherapy tolerance and for those with a wide range of immune system deficiencies, including autoimmunity disorders.

"We could not predict that prolonged fasting would have such a remarkable effect in promoting stem cell-based regeneration of the hematopoietic system," said corresponding author Valter Longo, the Edna M. Jones Professor of Gerontology and the Biological Sciences at the USC Davis School of Gerontology, and director of the USC Longevity Institute.

"When you starve, the system tries to save energy, and one of the things it can do to save energy is to recycle a lot of the immune cells that are not needed, especially those that may be damaged," Longo said. "What we started noticing in both our human work and animal work is that the white blood cell count goes down with prolonged fasting. Then when you re-feed, the blood cells come back. So we started thinking, well, where does it come from?"

Prolonged fasting forces the body to use stores of glucose, fat and ketones, but also breaks down a significant portion of white blood cells. Longo likens the effect to lightening a plane of excess cargo.

During each cycle of fasting, this depletion of white blood cells induces changes that trigger stem cell-based regeneration of new immune system cells. In particular, prolonged fasting reduced the enzyme PKA, an effect previously discovered by the Longo team to extend longevity in simple organisms and which has been linked in other research to the regulation of stem cell self-renewal and pluripotency that is, the potential for one cell to develop into many different cell types. Prolonged fasting also lowered levels of IGF-1, a growth-factor hormone that Longo and others have linked to aging, tumor progression and cancer risk.

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Fasting triggers stem cell regeneration of damaged, old immune system

Stem Cell Therapy Market by Treatment Mode & Therapeutic Applications – 2020 – Video


Stem Cell Therapy Market by Treatment Mode Therapeutic Applications - 2020
[196 Slides Report] Stem Cell Therapy Market report categories the Global market by Therapeutic Applications (CNS, CVS, Musculoskeletal, Wound Healing, GIT, Eye, Immune System), Treatment...

By: James Evans

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Stem Cell Therapy Market by Treatment Mode & Therapeutic Applications - 2020 - Video

torn rotator cuff/shoulder arthritis one year after stem cell therapy by Dr Harry Adelson – Video


torn rotator cuff/shoulder arthritis one year after stem cell therapy by Dr Harry Adelson
Richard discusses his outcome from bone marrow/adipose derived stem cells by Dr Harry Adelson for his torn rotator cuff and arthritic shoulder http://www.docereclinics.com.

By: Harry Adelson, N.D.

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torn rotator cuff/shoulder arthritis one year after stem cell therapy by Dr Harry Adelson - Video

Controversial stemcell treatment gets OK for toddler

'We'll administer Stamina tomorrow'

(ANSA) - Milan, June 6 - A controversial stem-cell treatment will once again be administered in an Italian hospital after being widely discredited, a pediatrician said Friday. "We've gotten the go-ahead from the (Brescia) hospital. Tomorrow at 10:00 we'll administer Stamina treatment" to a toddler suffering from a brain disease, said Dr. Marino Andolina, the vice president of the Stamina Foundation. The doctor, who will personally apply the treatment, said he received confirmation after a meeting with the head of Brescia's civic hospitals Ezio Belleri. Stamina's credibility has long been suspect, and last fall the health ministry ruled that the Stamina Foundation would no longer be allowed to test the treatment on humans. The foundation was also stripped of its non-profit status after a study found its treatment was "ignorant of stem-cell biology". Recent investigations have shown risks of the treatment range from nausea to cancer, and as many as one quarter of all patients treated have experienced "adverse effects". The head of the foundation, Davide Vannoni, may face indictment. But support from some patients who have used or requested the treatment remains strong, and a few days ago, a court in the central Marche region ruled that toddler Federico Mezzina could receive Stamina treatment for Krabbe disease.

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Controversial stemcell treatment gets OK for toddler

Stem Cells Treat Multiple Sclerosis in Mice

Human embryonic stem cells the bodys powerful master cells might be useful for treating multiple sclerosis, researchers reported Thursday.

A team has used cells taken from frozen human embryos and transformed them into a type of cell that scientists have hoped might help treat patients with MS, a debilitating nerve disease.

Mice with an induced version of MS that paralyzed them were able to walk freely after the treatment, the teams at Advanced Cell Technology and ImStem Biotechnology in Farmington, Connecticut, reported.

The cells appeared to travel to the damaged tissues in the mice, toning down the mistaken immune system response that strips the fatty protective layer off of nerve calls. Its that damage that causes symptoms ranging from tremors and loss of balance to blurry vision and paralysis.

These embryonic stem cells were carefully nurtured to make them form a type of immature cell called a mesenchymal stem cell. These cells worked better to treat the mice than naturally developed mesenchymal stem cells taken directly from bone marrow, the team wrote in the journal Stem Cell Reports, published by the International Society for Stem Cell Research.

The top mouse is paralyzed, while the mouse on the bottom was treated with human embryonic stem cells and is able to run around.

The company released a video to show the benefits. Untreated mice were suffering. They are paralyzed. They on their backs. They are dragging their limbs. They are in really sad shape, ACTs chief scientific officer, Dr. Bob Lanza, told NBC News.

Treated animals, they are walking and jumping around just like normal mice.

Lanza says human trials are many months away, but he thinks it will not be necessary to use controversial cloning technology to make perfectly matched human embryonic stem cells to treat patients.

We can use an off-the-shelf source and itll work for everyone, he said. So you can use them and not worry about rejection.

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Stem Cells Treat Multiple Sclerosis in Mice

Worldwide Leaders at DIA Annual Meeting to Discuss Hot Topics Facing Industry

WASHINGTON--(BUSINESS WIRE)--Hot topics facing drug development and accessevolving regulatory guidelines for novel therapies, a shifting pharmaceutical research and development (R&D) landscape, and U.S. regulatory challenges at home and overseaswill be discussed by global innovators at the DIA 2014 50th Annual Meeting, to be held at the San Diego Convention Center from June 15 to 19.

Todays thought leaders dedicated to accelerating health care delivery will have a unique opportunity to address these urgent issues with the brightest minds in medicine and regulation, said Barbara Lopez Kunz, DIAs global chief executive.

Research resulting in the first stem cells that are pluripotentmeaning they have the potential to transform into almost any cell in the bodywill be the backdrop for an examination of trends in regulation at the Pioneering Regenerative Medicine: Trends in Regulations for New Therapy session on June 16 at 8:30 a.m. Led by Shinji Miyake, professor of clinical research at Keio University School of Medicine in Japan, the discussion will review updated guidance to bring regenerative medicine to patients who need healthy tissue or organs.

The science of human stem cell research spans many regulatory jurisdictions of the Food and Drug Administration (FDA) and poses unique challenges for companies seeking to develop products safely. The forum on FDA Regulation of Therapeutic Products Derived From Human Stem Cells: Successfully Navigating the Regulatory Hurdles, to be held June 16 at 11 a.m., will feature leaders in research discussing the regulatory framework to govern stem cell products and how to improve interactions with FDA to bring the therapeutics to market.

Regulatory guidelines do not yet exist for 3-D printing, despite breakthroughs in producing new tissue and bones in this science-fiction-like arena. Steven Pollack, director of the FDAs Office of Science and Engineering Laboratories, will discuss the hurdles in approving 3-D printing products at the Health Cares Revolutionary Printing Press? 3-D Printing Blue Sky and Regulatory Path session, to be held June 17 at 10:30 a.m.

Domestic and international regulators are pushing for increased regulatory guidance of biosimilars, but the debate continues on how to tackle this emerging market of therapeutic products. On June 19 at 10:45 a.m., leaders in biosimilar innovation will provide a comparative analysis of the current global discussion about regulatory guidance at the Trends in Biosimilars Regulation Within Developed and Emerging Markets session, facilitated by Andrew Robertson, director of global regulatory policy at Merck & Co., Inc.

The industry is evolving from one dominated by large pharmaceutical companies and markets to an industry focused on smaller specialty companies and targeted medicines. Parts one and two of The Changing Landscape for Bioinnovation: The Emergence of Small Pharma, Strategic Alliances, and Precision Medicine will discuss navigating the new environment and the potential impact on R&D. The first session will be held June 17 at 8 a.m., and the second will follow at 10:30 a.m.

Christopher Hickey, director of the FDAs office in China, will discuss efforts to increase the number of inspectors in China in a rapidly expanding global drug market during the Challenges and Opportunities Facing FDAs International Posts session, to be held June 18 at 1:30 p.m. Topics will include increasing FDAs regulatory staff in 11 locations worldwide, implementing quality manufacturing systems, dealing with inconsistencies in regulatory oversight among nations and obtaining visa approvals.

ABOUT DIA:DIA is the global connector in the life sciences product development process. Our association of more than 18,000 members builds productive relationships by bringing together regulators, innovators, and influencers to exchange knowledge and collaborate in a neutral setting. DIAs network creates unparalleled opportunities for the exchange of knowledge and has the interdisciplinary experience to prepare for future developments. DIA is an independent, nonprofit organization with its global center in Washington, D.C., USA, and regional offices covering North and South America (Horsham, Pa., USA); Europe, North Africa and the Middle East (Basel, Switzerland); and Japan (Tokyo), India (Mumbai) and China (Beijing). For more information, visitwww.diahome.org.

ABOUT DIAs 2014 50th ANNUAL MEETING:Celebrate the Past Invent the Future is the largest multidisciplinary event that brings together a community of life sciences professionals at all levels and across all disciplines involved in the discovery, development and life cycle management of medical products. The meeting aims to foster innovation that will lead to the development of safe and effective medical products and therapies for patients.For more information, visitwww.diahome.org/dia2014.

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Worldwide Leaders at DIA Annual Meeting to Discuss Hot Topics Facing Industry

University of Michigan Stem Cell Research | Overview

The University of Michigan has recently emerged as a national leader in the three main types of stem cell research: embryonic, adult, and reprogrammed cells known as iPS cells.

A long-time leader in the study of adult stem cells, U-M has bolstered its human embryonic stem cell program, and added a complementary iPS cell research effort, since the passage of Proposal 2 in November 2008. The state constitutional amendment eased onerous restrictions on the types of embryonic stem cell research allowed in Michigan.

Recent milestones include:

In addition to the work underway by the Consortium for Stem Cell Therapies, hubs for U-M stem cell research also exist at the Life Science Institutes Center for Stem Cell Biology and at the U-M Health Systems Comprehensive Cancer Center. Other groundbreaking stem cell work is being pursued at other units across campus.

The Center for Stem Cell Biology was established in 2005 with $10.5 million provided by the U-M Medical School, the Life Sciences Institute, and the Molecular and Behavioral Neurosciences Institute.

The centers main goal is to determine the fundamental mechanisms that regulate stem cell function. That knowledge, in turn, provides new insights into the origins of disease and suggests new approaches to disease treatment. Most of the work involves adult stem cells including blood-forming and nervous system stem cells but human embryonic stem cells also are studied.

The U-M Comprehensive Cancer Center is one of the few places in North America that has made an institutional commitment to cancer stem cell research. Cancer stem cells are responsible for triggering the uncontrolled cell growth that leads to malignant tumors.

U-M researchers were the first to identify stem cells in solid tumors, finding them in breast cancer in 2003. They were also the first to find pancreatic and head-and-neck stem cells. At the U-M cancer center, scientists are investigating how these cells mutate, causing unregulated growth that ultimately leads to cancer.

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University of Michigan Stem Cell Research | Overview

Stem Cells Successfully Transplanted And Grown In Pigs

June 5, 2014

Nathan Hurst, University of Missouri

One of the biggest challenges for medical researchers studying the effectiveness of stem cell therapies is that transplants or grafts of cells are often rejected by the hosts. This rejection can render experiments useless, making research into potentially life-saving treatments a long and difficult process. Now, researchers at the University of Missouri have shown that a new line of genetically modified pigs will host transplanted cells without the risk of rejection.

The rejection of transplants and grafts by host bodies is a huge hurdle for medical researchers, said R. Michael Roberts, Curators Professor of Animal Science and Biochemistry and a researcher in the Bond Life Sciences Center. By establishing that these pigs will support transplants without the fear of rejection, we can move stem cell therapy research forward at a quicker pace.

In a published study, the team of researchers implanted human pluripotent stem cells in a special line of pigs developed by Randall Prather, an MU Curators Professor of reproductive physiology. Prather specifically created the pigs with immune systems that allow the pigs to accept all transplants or grafts without rejection. Once the scientists implanted the cells, the pigs did not reject the stem cells and the cells thrived. Prather says achieving this success with pigs is notable because pigs are much closer to humans than many other test animals.

Many medical researchers prefer conducting studies with pigs because they are more anatomically similar to humans than other animals, such as mice and rats, Prather said. Physically, pigs are much closer to the size and scale of humans than other animals, and they respond to health threats similarly. This means that research in pigs is more likely to have results similar to those in humans for many different tests and treatments.

Now that we know that human stem cells can thrive in these pigs, a door has been opened for new and exciting research by scientists around the world, Roberts said. Hopefully this means that we are one step closer to therapies and treatments for a number of debilitating human diseases.

Roberts and Prather published their study, Engraftment of human iPS cells and allogeneic porcine cells into pigs with inactivated RAG2 and accompanying severe combined immunodeficiency in the Proceedings of the National Academy of Sciences.

Source: Nathan Hurst, University of Missouri

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Stem Cells Successfully Transplanted And Grown In Pigs