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Stem Cells Show Promise in Reducing Hardening of the Arteries

Posted: December 11, 2014 at 7:53 pm

Durham, NC (PRWEB) December 10, 2014

The medical world is excited about the potential that stem cells have demonstrated in aiding the recovery of patients who have suffered a heart attack. Now, a new study appearing in the January issue of STEM CELLS Translational Medicine indicates that stem cells may also benefit those who suffer from hardening of the arteries.

Hardening of the arteries or atherosclerosis occurs due to a buildup of fats, cholesterol and other substances in and on the artery walls. The arteries become hardened by fibrous tissue and calcification and, as the plaque grows, it clogs the artery tubes, reducing the oxygen and blood supply to the affected organ. If the artery becomes severely blocked, it can cause death of the tissue fed by the artery and lead to a heart attack or stroke.

Based on the success of mesenchymal stem cells (MSCs) in treating a heart attack, Shih-Chieh Hung, M.D, Ph.D., of the Department of Medical Research, Taipei Veterans General Hospital, Taiwan, led a team of researchers who wanted to learn if MSCs transplanted in a patient in the early stage of atherosclerosis might prevent the diseases development and/or progression. MSCs are stem cells that can be collected from many adult tissues and differentiate into various cell types, including cartilage, bone, tendons, muscle and skin.

The team began by examining the effects of MSCs on inhibiting atherosclerosis in human/mouse endothelial cells treated with oxidized low-density lipoprotein (oxLDL) in a lab dish. The endothelium is the thin layer of cells that lines the interior surface of blood vessels and lymphatic vessels, forming an interface between circulating blood and the rest of the vessel wall.

Then we moved on to see how they might affect live mice that had been fed a high-fat diet, Dr. Hung said. We found that the MSCs transplantation improved endothelial function and reduced the plaque formation in the lab cells as well as in the high fat-diet fed mice. This leads us to believe that MSCs might prove useful someday in treating atherosclerosis in human patients, he noted.

Dr. Hung said that the next step is to identify ways to maintain the beneficial effect of MSCs for a long time, as well as learn more about the complex mechanism underlying the MSCs transplantation in different stages of atherosclerosis.

This study was aimed at intervening in the early stages of disease development to prevent further progression, said Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. It is the first study to show that in animals, stem cells can treat atherosclerosis by repairing the blood vessel lining.

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The article, Mesenchymal Stem Cells Ameliorate Atherosclerotic Lesions Via Restoring Endothelial Function, can be accessed online at http://www.stemcellsTM.com

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Stem Cells Show Promise in Reducing Hardening of the Arteries

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Mechanical cues reprogram normal cell lines into stem-like cells

Posted: December 11, 2014 at 7:49 pm

Scientists at UB and other institutions have turned cells normally used as model cells, known as immortalized cells, into stem or, as they call it, stem-like cells, using nothing more than mechanical stress. They have done it without employing the potentially hazardous techniques previously used to obtain similar results.

The researchers use the term stem-like cells to describe cells in tissue culture that have many of the biochemical markers of stem cells. Determining whether or not they can differentiate will be the focus of future research.

The finding is described in a paper published recently online before print in the Proceedings of the National Academy of Sciences. The researchers discovered that changing the mechanical stresses on neuronal and other cell types in tissue culture allowed them to be reprogrammed into stem-like cells.

Normal cell types in tissue culture are spread out and have differentiated internal structures, but changing cell mechanics caused the cells to turn into clusters of spherical cells that had many of the biochemical markers of cells, says Frederick Sachs, SUNY Distinguished Professor in the Department of Physiology and Biophysics and senior author.

The stem cell advance was made possible by the development of a genetically encoded optical probe by Fanje Meng, research assistant professor in the Department of Physiology and Biophysics and lead UB author. The probe measures the mechanical stress in actin, a major structural protein present in all cells. Actin is involved in muscle contraction and numerous cellular processes, including cell signaling, how cells are shaped and how they move.

The actin probes will provide researchers with a method of studying how mechanical forces influence living cells, tissues, organs and animals in real time.

This probe allows us, for the first time, to measure the stress in actin within living cells, explains Sachs. We saw gradients of stress in actin filaments even in single living cells.

Much of existing biomechanics will have to be rethought, since many studies have assumed that the stresses are uniform, Sachs continues. The actin stress probe showed that the tension in actin fibers in stem cells is higher than in normal cells. That was very surprising to us.

He adds that while mechanics are well known to have a role in cellular processes, the details are poorly understood because there have been few ways to measure the stress in specific proteins. A clinically relevant example is that metastatic cancer cells, the fatal variety, have different mechanics than cells of the parent tumor.

This probe will allow cancer researchers to better understand what allows cells to become metastatic, says Sachs.

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Mechanical cues reprogram normal cell lines into stem-like cells

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Researchers show how stem cells can be reprogrammed

Posted: December 11, 2014 at 7:48 pm

TORONTO A Canadian-led international team of researchers has begun solving the mystery of just how a specialized cell taken from a persons skin is reprogrammed into an embryonic-like stem cell, from which virtually any other cell type in the body can be generated.

The research is being touted as a breakthrough in regenerative medicine that will allow scientists to one day harness stem cells to treat or even cure a host of conditions, from blindness and Parkinsons disease to diabetes and spinal cord injuries.

Besides creating the reprogramming roadmap, the scientists also identified a new type of stem cell, called an F-class stem cell due to its fuzzy appearance. Their work is detailed in five papers published Wednesday in the prestigious journals Nature and Nature Communications.

Dr. Andras Nagy, a senior scientist at Mount Sinai Hospital in Toronto, led the team of 50 researchers from Canada, the Netherlands, South Korea and Australia, which spent four years analyzing and cataloguing the day-by-day process that occurs in stem cell reprogramming.

The work builds on the 2006-2007 papers by Shinya Yamanaka, who showed that adult skin cells could be turned into embryonic-like, or pluripotent, stem cells through genetic manipulation, a discovery that garnered the Japanese scientist the Nobel Prize in 2012.

Nagy likened the roughly 21-day process to complete that transformation to a black box, so called because scientists did not know what went on within the cells as they morphed from one cell type into the other.

It was just like a black box, Nagy said Wednesday, following a briefing at the hospital. You start with a skin cell, you arrive at a stem cell but we had no idea what was happening inside the cell.

Nagys team set about cataloguing the changes as they occurred by removing cells from culture dishes at set points during the three-week period, then analyzing such cellular material as DNA and proteins present at that moment.

The result is a database that will be available to scientists around the world, which the team hopes will spur new research to advance the field of stem cell-based regenerative medicine.

Co-author Ian Rogers, a scientist in Nagys lab, said the database will allow researchers to identify various properties of the developing stem cells, which could mean improving their ability to treat or cure disease.

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Researchers show how stem cells can be reprogrammed

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R3 Stem Cell Welcomes Beverly Hills Pain Specialists Dr. George Graf as a Featured Regenerative Medicine Doctor

Posted: December 11, 2014 at 7:47 pm

Beverly Hills, CA (PRWEB) December 11, 2014

R3 Stem Cell is proud to welcome Dr. George Graf as a Featured Regenerative Medicine Doctor in the Los Angeles and Beverly Hills area. Dr. Graf is a first rate pain management doctor, who offers several types of stem cell procedures and platelet rich plasma therapy for all types of spinal conditions such as neck and back pain, arthritis, disc degeneration and more. Those interested should call (844) GET-STEM for more information and scheduling.

R3 Stem Cell is a nationwide provider of regenerative medicine products and education for both doctors and patients. The company only works with the top doctors and practices in the field of stem cell therapy. Dr. Graf is Double Board Certified and is very highly regarded by his peers and patients.

The conditions Dr. Graf treats include degenerative disc disease, spinal arthritis, scoliosis, neuropathy, failed back surgery syndrome and more. Regenerative medicine offers the potential to not only bring pain relief, but also help repair and regenerate damaged tissue.

Along with Dr. Graf being a regenerative medicine expert in the LA and Beverly Hills area, R3 also works with Dr. Raj. Dr. Raj is a Double Board Certified orthopedic specialist, who offers regenerative medicine procedures for rotator cuffs, hip and knee arthritis, sports injuries and much more. Between Dr. Graf and Dr. Raj, the whole body is covered for treatments.

All of the treatment options are outpatient and very low risk. Platelet Rich Plasma Therapy involves a person's own blood, which is immediately processed and injected into the problem area. Bone marrow derived stem cell therapy involves an aspiration from one's iliac crest, with the material being processed to concentrate stem cells and then inject into the problem area. Additionally, amniotic stem cells are offered, with the fluid being obtained from a consenting donor undergoing a scheduled C-section. The fluid is processed at an FDA regulated lab and no fetal tissue is involved whatsoever.

To date, several small studies have shown excellent benefit with regenerative medicine procedures. This has been extremely encouraging, and allowed stem cell therapy to exponentially increase in popularity nationwide. R3 Stem Cell is at the forefront in regenerative medicine, teaming with the top doctors such as Drs. Raj and Graf to help patients achieve pain relief and avoid surgery.

Call (844) GET-STEM today for more information and scheduling with a top stem cell doctor today.

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R3 Stem Cell Welcomes Beverly Hills Pain Specialists Dr. George Graf as a Featured Regenerative Medicine Doctor

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Canadian scientists crack stem cell reprogramming code

Posted: December 11, 2014 at 2:54 pm

By Sheryl Ubelacker The Canadian Press

WATCH: Dr. Andras Nagy describes the scientific breakthrough he led in solving the mystery of the stem cell reprogramming code.

It was just like a black box, Nagy said Wednesday, following a briefing at the hospital. You start with a skin cell, you arrive at a stem cell but we had no idea what was happening inside the cell.

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Canadian scientists crack stem cell reprogramming code

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Stem cells: The black box of reprogramming

Posted: December 11, 2014 at 2:54 pm

Nik Spencer/Nature

Eggs and sperm do it when they combine to make an embryo. John Gurdon did it in the 1960s, when he used intestinal cells from tadpoles to generate genetically identical frogs. Ian Wilmut did it too, when he used an adult mammalian cell to make Dolly the sheep in 1996. Reprogramming reverting differentiated cells back to an embryonic state, with the extraordinary ability to create all the cells in the body has been going on for a very long time.

Scientific interest in reprogramming rocketed after 2006, when scientists showed that adult mouse cells could be reprogrammed by the introduction of just four genes, creating what they called induced pluripotent stem (iPS) cells1. The method was simple enough for almost any lab to attempt, and now it accounts for more than a thousand papers per year. The hope is that pluripotent cells could be used to repair damaged or diseased tissue something that moved closer to reality this year, when retinal cells derived from iPS cells were transplanted into a woman with eye disease, marking the first time that reprogrammed cells were transplanted into humans (see Nature http://doi.org/xhz; 2004).

There is just one hitch. No one, not even the dozen or so groups of scientists who intensively study reprogramming, knows how it happens. They understand that differentiated cells go in, and pluripotent cells come out the other end, but what happens in between is one of biology's impenetrable black boxes. We're throwing everything we've got at it, says molecular biologist Knut Woltjen of the Center for iPS Cell Research and Application at Kyoto University in Japan. It's still a really confusing process. It's very complicated, what we're doing.

Kerri Smith talks to researcher Andras Nagy and reporter David Cyranoski about reprogramming cells.

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One of the problems, stem-cell biologists say, is that their starting population contains a mix of cells, each in a slightly different molecular state. And the process for making iPS cells is currently inefficient and variable: only a tiny fraction end up fully reprogrammed and even these may differ from one another in subtle but important ways. What is more, the path to reprogramming may vary depending on the conditions under which cells are being grown, and from one lab to the next. This makes it difficult to compare experimental results, and it raises safety concerns should a mix of poorly characterized cells be used in the clinic.

But new techniques are starting to clarify the picture. By carrying out meticulous analyses of single cells and amassing reams of detailed molecular data, biologists are identifying a number of essential events that take place en route to a reprogrammed state. This week, the biggest such project an international collaboration audaciously called Project Grandiose unveiled its results26. The scientists involved used a battery of tests to take fine-scale snapshots of every stage of reprogramming and in the process, revealed an alternative state of pluripotency. It was the first high-resolution analysis of change in cell state over time, says Andras Nagy, a stem-cell biologist at Mount Sinai Hospital in Toronto, Canada, who led the project. I'm not shy about saying grandiose.

I'm not shy about saying grandiose.

But there is more to do if scientists want to control the process well enough to generate therapeutic cells with ease. Yes, we can make iPS cells and yes we can differentiate them, but I think we feel that we do not control them enough says Jacob Hanna, a stem-cell biologist at the Weizmann Institute of Science in Rehovot, Israel. Controlling cell behaviour at will is very cool. And the way to do it is to understand their molecular biology with great detail.

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Stem cells: The black box of reprogramming

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Novel approach for estrogen-receptor-positive breast cancer reported

Posted: December 11, 2014 at 2:53 pm

PUBLIC RELEASE DATE:

10-Dec-2014

Contact: Nora Dudley nodudley@lumc.edu 708-216-6268 Loyola University Health System @LoyolaHealth

Loyola researchers and collaborators have reported promising results from a novel therapeutic approach for women with estrogen-receptor-positive breast cancer.

The new approach, a new drug class called gamma secretase inhibitors (GSI), specifically inhibits Notch and shuts down critical genes and cancer cells responsible for tumor growth.

Kathy Albain, MD, FACP, who led the study, will present findings Dec. 11 during the 2014 San Antonio Breast Cancer Symposium.

Existing cancer drugs are effective in killing mature breast cancer cells. But a handful of immature breast cancer stem cells are resistant to such drugs. They survive and are responsible for tumor growth and progression. Resistance to standard therapy is a major cause of death in women with estrogen-receptor-positive breast cancer. Approximately 75 percent of breast cancers are estrogen-receptor positive.

"New treatments are desperately needed for women with estrogen-receptor-positive breast cancer who develop resistance to standard therapies," said Dr. Albain, a professor in the Department of Medicine, Division of Hematology/Oncology at Loyola University Chicago Stritch School of Medicine. "Our research suggests a potential role this new experimental drug class may have in optimizing existing endocrine therapies, such a tamoxifen and aromatase inhibitors, and in overcoming resistance to cancer drugs."

The Notch protein promotes tumor growth and survival. The protein is present on the surface of cancer stem cells. The protein latches on to other cells, and the resulting "molecular handshake" activates various genes in the stem cells that drive tumor growth, spread and survival. Activating these genes, in effect, makes the stem cells resistant to common cancer drugs. A pilot study conducted at Loyola found that the GSI appears to block this process by turning off key genes.

The purpose of the study was to identify critical genes involved in the process. The study included 20 patients with early-stage, estrogen-receptor-positive breast cancer. Prior to surgery, the patients received one of two commonly used drugs, tamoxifen or letrozole, for 14 days to block the estrogen stimulation of breast cancer cells. They underwent a biopsy on day 14. They then received the GSI, MK-0752, plus continued one of two standard drugs, tamoxifen or letrozole. Patients underwent their definitive breast cancer surgery on day 25 and part of this tumor was provided as well for this research.

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Novel approach for estrogen-receptor-positive breast cancer reported

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NYSCF and the CMTA enter collaboration to advance neuropathies research

Posted: December 11, 2014 at 2:53 pm

PUBLIC RELEASE DATE:

10-Dec-2014

Contact: David McKeon dmckeon@nyscf.org 212-365-7440 New York Stem Cell Foundation @nyscf

New York, NY (December 10, 2014) - The New York Stem Cell Foundation (NYSCF) Research Institute, a non-profit organization dedicated to accelerating cures through stem cell research, announced a collaboration today with the Charcot-Marie-Tooth Association (CMTA), a patient-led disease foundation with the mission to advance research on genetic neuropathies that leads to the development of new therapies. The immediate aim of the collaboration is to develop a bank of induced pluripotent stem cell (iPSC) lines for a variety of neuropathy disorders of known genetic causation and to eventually develop personalized drug therapies.

NYSCF will make stem cells lines from Charcot-Marie-Tooth patient materials that have been curated in a biobank assembled by Dr. Michael Shy at the University of Iowa, a member of the CMTA STAR consortium of sponsored investigators. Utilizing its automated technology, the NYSCF Global Stem Cell ArrayTM, NYSCF will systematically generate iPSC lines from tissue samples obtained from patients representing a number of disease states. These cell lines will then be used to develop methods for creating differentiated cells that mimic the myelin-producing Schwann cells that are defective in Type 1 Charcot-Marie-Tooth (CMT) disorders of peripheral nerve, as well as the motor and sensory neurons that are defective in Type 2 disorders. Members of the STAR consortium currently engaged in this CMTA-sponsored effort to differentiate iPSC lines include Dr. Robert Baloh, Cedar-Sinai Medical Center, and Dr. Gabsang Lee, Johns Hopkins University. The ultimate aim of this research is to create a personalized medicine approach to rapid testing of human drug responsiveness in a dish. The iPSC lines will also be expanded and banked by NYSCF and made available to the global scientific community to be used for research and the development of therapies.

Patrick Livney, CEO of the CMTA notes: "The Foundation has assembled the scientific and clinical key opinion leaders in CMT disorders, and the research tools necessary to validate therapeutic opportunities for their clinical potential. We have set out to engage drug makers to work together with the CMTA to advance new therapeutic approaches to our patients, and our STAR network that combines this world class research expertise with an operational capability has been highly enabling to the formation of collaborative alliances for this purpose. Currently, there are no therapies for the different CMT disorders to halt either the onset or progression of the disease. This NYSCF collaboration represents an exciting opportunity for the CMTA to place research on therapies for Charcot-Marie-Tooth disorders in a personalized, patient context at a very early stage.

"We are very exctied to partner with the Charcot-Marie-Tooth Association to develop resources that will enable the pursuit of new treatments and eventually cures for neruropathy disorders," said Susan L. Solomon, Co-Founder and CEO of NYSCF. "Partnering with CMTA provides us with the necessary community of scientists, patients, disease experts, as well as resources that allows us to move research forward. We believe that this type of interdisciplinary collaboration between various stakeholders is essential to to move research forward in the pursuit of cures."

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About Charcot-Marie-Tooth Association

The Charcot-Marie-Tooth Association (CMTA) is a registered 501c3 dedicated to serving an international patient community that suffers from rare and disabling neuropathies of genetic origin. The Foundation directly engages its STAR scientific and clinical research network in the identification, validation and clinical development of therapies for the different Charcot-Marie-Tooth disorders.

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R3 Stem Cell Welcomes Beverly Hills Pain Specialists Dr …

Posted: December 11, 2014 at 2:51 pm

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Discovery links shift in metabolism to stem cell renewal

Posted: December 11, 2014 at 2:51 pm

Dec 10, 2014 When study authors Bryce Carey (left) and Lydia Finley (right) exposed mouse embryonic stem cells to an important metabolite, those cells became more likely to renew themselves, appearing as pink colonies on the screen. That metabolite, alpha-ketoglutarate, is also known to be involved in regulating so-called epigenetic marks that control the expression of genes. This is one of the first demonstrations that a metabolite can influence the fate of stem cells. Credit: Zach Veilleux / The Rockefeller University

Stem cells in early embryos have unlimited potential; they can become any type of cell, and researchers hope to one day harness this rejuvenating power to heal disease and injury. To do so, they must, among other things, figure out how to reliably arrest stem cells in a Peter Pan-like state of indefinite youth and potential. It's clear the right environment can help accomplish this, acting as a sort of Neverland for stem cells. Only now are scientists beginning to understand how.

New collaborative research between scientists at Rockefeller University and Memorial Sloan Kettering Cancer Center offers an explanation: Stem cells can rewire their metabolism to enhance an erasure mechanism that helps them avoid committing to a specific fate; in turn, this improves stem cells' ability to renew themselves.

Experiments described today (December 10) in Nature link metabolism, chemical reactions that turn food into energy and cellular building materials, with changes to how genes are packaged, and, as a result, read. It turns out that by skewing their metabolism to favor a particular product, stem cells can keep their entire genome accessible and so maintain their ability to differentiate into any adult cell.

"All of the principal enzymes charged with modifying DNA as well as DNA-histone protein complexes called chromatin use the products of cellular metabolism to do so. But how specific alterations in metabolic pathways can impact gene expression programs during development and differentiation has remained a mystery," says lead researcher C. David Allis, Joy and Jack Fishman Professor and head of the Laboratory of Chromatin Biology and Epigenetics. "This collaborative effort with Craig Thompson's lab at Memorial Sloan Kettering reveals that the nutrients a stem cell uses, and how it uses them, can contribute to a cell's fate by changing the chromatin landscape and, as a result, influencing gene expression."

These changes are epigenetic, meaning they do not affect genes themselves, instead they alter how DNA is packaged, making it more or less accessible for expression. In this case, researchers were interested in a specific type of epigenetic change: chemical groups, known as methyl groups, that attach to chromatin. Generally, the addition of these methyl groups compacts and silences regions of the genome. To maintain their ability to give rise to any type of cell in the body, stem cells need all of their genome available, and so they must keep methylation in check.

Some epigenetic marks, such as methyl groups, are themselves products of metabolism - metabolites. What's more some other metabolites participate in the reactions that remove methylations, making genes available for expression. After joining the Allis Lab, postdoc Bryce Carey presented an idea that tied these concepts together: "What if in stem cells the changes to chromatin reflect a unique metabolism that helps to drive reactions that help to keep chromatin accessible? This connection would explain how embryonic stem cells are so uniquely poised to activate so much of their genomes," Carey says.

Mouse embryonic stem cells grown in a medium known as 2i are much better at renewing themselves than those grown in the traditional medium containing bovine serum, although researchers don't fully understand why. Carey and co-first author Lydia Finley, a postdoc in Thompson's metabolism-focused lab, compared the metabolism of cells grown in both media.

Carey and Finley first noticed that the 2i cells did not require glutamine, an amino acid most cells need to make the metabolite alpha-ketoglutarate, an important player in a series of metabolic reactions known as the citric acid cycle and a metabolite that had also been previously implicated in regulation of methylations on chromatin. Even without glutamine, however, the 2i cells managed to produce significant amounts of alpha-ketoglutarate.

To their surprise, 2i cells had rewired their metabolism to reduce the breakdown of alpha-ketoglutarate in the citric acid cycle, where an enzyme normally converts alpha-ketoglutarate to succinate to fuel cell growth. This resulted in increased alpha-ketoglutarate to fuel the reactions that erase methyl groups from chromatin.

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Discovery links shift in metabolism to stem cell renewal