Category Archives: Stem Cells

Released: 19-Aug-2014 11:30 AM EDT Embargo expired: 21-Aug-2014 12:00 PM EDT Source Newsroom: Johns Hopkins Medicine Contact Information

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Newswise Johns Hopkins stem cell biologists have found a way to reprogram a patients skin cells into cells that mimic and display many biological features of a rare genetic disorder called familial dysautonomia. The process requires growing the skin cells in a bath of proteins and chemical additives while turning on a gene to produce neural crest cells, which give rise to several adult cell types. The researchers say their work substantially expedites the creation of neural crest cells from any patient with a neural crest-related disorder, a tool that lets physicians and scientists study each patients disorder at the cellular level.

Previously, the same research team produced customized neural crest cells by first reprogramming patient skin cells into induced pluripotent stem (iPS) cells, which are similar to embryonic stem cells in their ability to become any of a broad array of cell types.

Now we can circumvent the iPS cells step, saving seven to nine months of time and labor and producing neural crest cells that are more similar to the familial dysautonomia patients cells, says Gabsang Lee, Ph.D., an assistant professor of neurology at the Institute for Cell Engineering and the studys senior author. A summary of the study will be published online in the journal Cell Stem Cell on Aug. 21.

Neural crest cells appear early in human and other animal prenatal development, and they give rise to many important structures, including most of the nervous system (apart from the brain and spinal cord), the bones of the skull and jaws, and pigment-producing skin cells. Dysfunctional neural crest cells cause familial dysautonomia, which is incurable and can affect nerves ability to regulate emotions, blood pressure and bowel movements. Less than 500 patients worldwide suffer from familial dysautonomia, but dysfunctional neural crest cells can cause other disorders, such as facial malformations and an inability to feel pain.

The challenge for scientists has been the fact that by the time a person is born, very few neural crest cells remain, making it hard to study how they cause the various disorders.

To make patient-specific neural crest cells, the team began with laboratory-grown skin cells that had been genetically modified to respond to the presence of the chemical doxycycline by glowing green and turning on the gene Sox10, which guides cells toward maturation as a neural crest cell.

Testing various combinations of molecular signals and watching for telltale green cells, the team found a regimen that turned 2 percent of the cells green. That combination involved turning on Sox10 while growing the cells on a layer of two different proteins and giving them three chemical additives to rewind their genetic memory and stimulate a protein network important for development.

Analyzing the green cells at the single cell level, the researchers found that they showed gene activity similar to that of other neural crest cells. Moreover, they discovered that 40 percent were quad-potent, or able to become the four cell types typically derived from neural crest cells, while 35 percent were tri-potent and could become three of the four. The cells also migrated to the appropriate locations in chick embryos when implanted early in development.

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Biologists Reprogram Skin Cells to Mimic Rare Disease

Durham, NC (PRWEB) August 22, 2014

Human induced pluripotent stem cells (hiPSCs) have great potential in the field of regenerative medicine because they can be coaxed to turn into specific cells; however, the new cells dont always act as anticipated. They sometimes mutate, develop into tumors or produce other negative side effects. But in a new study recently published in STEM CELLS Translational Medicine, researchers appear to have found a way around this, simply by removing the material used to reprogram the stem cell after they have differentiated into the desired cells.

The study, by Ken Igawa, M.D., Ph.D., and his colleagues at Tokyo Medical and Dental University along with a team from Osaka University, could have significant implications both in the clinic and in the lab.

Scientists induce (differentiate) the stem cells to become the desired cells, such as those that make up heart muscle, in the laboratory using a reprogramming transgene that is, a gene taken from one organism and introduced into another using artificial techniques.

We generated hiPSC lines from normal human skin cells using reprogramming transgenes, then we removed the reprogramming material. When we compared the transgene-free cells with those that had residual transgenes, both appeared quite similar, Dr. Igawa explained. However, after the cells differentiation into skin cells, clear differences were observed.

Several types of analyses revealed that the keratinocytes cells that make up 90 percent of the outermost skin layer that emerged from the transgene-free hiPSC lines were more like normal human cells than those coming from the hiPSCs that still contained some reprogramming material.

These results suggest that transgene-free hiPSC lines should be chosen for therapeutic purposes, Dr. Igawa concluded.

Human induced pluripotent stem cell (hiPSC) lines have potential for therapeutics because of the customized cells and organs that can potentially be induced from such cells, Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. This study illustrates a potentially powerful approach for creating hiPSCs for clinical use.

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The full article, Removal of Reprogramming Transgenes Improves the Tissue Reconstitution Potential of Keratinocytes Generated From Human Induced Pluripotent Stem Cells, can be accessed at http://stemcellstm.alphamedpress.org/content/early/2014/07/14/sctm.2013-0179.abstract.

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Removing Programming Material After Inducing Stem Cells Could Improve Their Regeneration Ability

Bishop David Zubik of the Catholic Diocese of Pittsburgh is taking the ice bucket challenge to help find a cure for Lou Gehrig's disease, but he is giving a cold shoulder to the ALS Association, the usual beneficiary.

We are aware of the ALS Association and how it uses at least in one of its areas of research embryonic stem cells, said the Rev. Ronald Lengwin, spokesman for the diocese.

Lengwin said the bishop intends to make a donation to the John Paul II Medical Research Institute, which uses a variety of adult stem cells to find cures and therapies for various diseases, he said. They do not engage in embryonic stem cell research of any kind.

He declined to say how much the bishop was contributing.

The superintendent of Catholic schools in the Archdiocese of Cincinnati discouraged schools from taking part in the popular fundraiser unless they gave the money raised to groups that fight ALS without using embryonic stem cells.

Lengwin said the church opposes research using embryonic stem cells because they're used with part of the destruction of life, often with a child that has been aborted.

The ALS Association said it supports a study using embryonic stem cells but said donors can require that their gifts go elsewhere.

The bishop is taking part on behalf of the Rev. Dennis Colamarino, pastor of Christ the Light of the World Parish and St. Joseph's parishes in Duquesne. Colamarino was diagnosed with Amyotrophic Lateral Sclerosis or ALS, a neurodegenerative disease, a year ago. About 30,000 Americans have the disease.

After an 11 a.m. Mass on Saturday at Holy Name Church of Christ the Light of the World Parish, police will close South First Street in Duquesne, and Zubik and Colamarino will be doused with ice and water.

I see this as an opportunity to give back some of the love and support that I have received over the last 15 months, Colamarino said in a prepared statement.

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Pittsburgh bishop throws cold water on ALS group, which uses embryonic stem cells

21.08.2014 - (idw) Schweizerischer Nationalfonds SNF

Up until puberty, the pancreas is more adaptable and possesses a greater potential for self-healing than had previously been assumed. This is the conclusion reached by a study with mice funded through the National Research Programme "Stem Cells and Regenerative Medicine" (NRP 63). Approximately 40,000 persons in Switzerland suffer from type-1 diabetes. The illness is caused by the loss of so-called pancreatic beta cells, the cells that produce the hormone insulin, which is essential for regulating the use of sugar in the body. Since beta cells do not regenerate, scientists have traditionally assumed that the loss of these cells is irreversible; indeed, diabetic patients require insulin injections for life.

Previously unknown mechanism

Four years ago, the research team of Pedro Herrera (University of Geneva) first cast doubt on this assumption when they demonstrated that a few alpha cells in the pancreas of genetically modified diabetic mice changed into beta cells. Alpha cells normally produce the blood sugar-raising hormone glucagon, but in diabetic mice they started producing insulin instead. Herrera's team has now made a second discovery, which has just been published in the journal "Nature" (*): in prepubescent mice the pancreas is capable of compensating the loss of insulin-producing beta cells. "This is achieved by a mechanism unknown until now," says Herrera. The process involves the reversion of delta cells (which produce somatostatin, another pancreatic hormone) to a precursor-like cell state, with proliferation and later reconstitution of the populations of beta and delta cells.

In contrast to the conversion of alpha cells, which only concerns a small fraction of the alpha cell population, the new mechanism involving delta cell fate change is a more efficient way of offsetting the loss of beta cells and thus diabetes recovery. Yet while alpha cells can reprogram into insulin production also in old mice, the ability of delta cells to do so is limited and does not extend beyond puberty.

Although Herrera's group has investigated the versatility of pancreatic cells in mice, several observations in diabetic patients suggest that the human pancreas is capable of transformation too. "The new mechanism shows that the pancreas is much more plastic and at least during childhood possesses a much greater potential for self-healing than we had previously assumed," says Herrera. There is still a long way to go before diabetes patients might be able to benefit from these findings, but the discovery that delta cells have a high degree of plasticity points to a hitherto unsuspected option for therapeutic intervention.

(*) S. Chera, D. Baronnier, L. Ghila, V. Cigliola, J. N. Jensen, G. Gu, K. Furuyama, F. Thorel, F. M. Gribble, F. Reimann and P. L. Herrera (2014). Diabetes Recovery By Age-Dependent Conversion of Pancreatic Delta-Cells Into Insulin Producers. Nature online: doi: 10.1038/nature13633 (Journalists can obtain a pdf file from the SNSF by writing to: com@snf.ch)

National Research Programme

"Stem Cells and Regenerative Medicine" (NRP 63) The aim of NRP 63 is to obtain basic information about the nature, functioning and convertibility of stem cells. NRP 63 also hopes to strengthen stem cell research in Switzerland. It was launched in 2010 and comprises 12 projects. NRP 63 has a budget of CHF 10 million and is scheduled to end next year.

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Astonishing regeneration potential of the pancreas

Because the ALS Association supports stem-cell research.

The Ice Bucket Challenge has been the biggest viral-charity sensation of the year, and maybe ever reaching its cold, wet arms all the way to George W. Bush and Anna Wintour, and raising millions of dollars for ALS research along with providing an immaculate blooper reel.

But one group is not pleased by all your Facebook videos: anti-abortion activists, who are mad that the ALS Association gives money to a group that supports stem-cell research.

"Attention pro-lifers: be careful where you send your ALS Ice Bucket Challenge donation," blared a headline on LifeNews.com earlier this week. The article explained that the ALS Association, one of the charities receiving ice-bucket donations, gave $500,000 last year to the Northeast ALS Consortium, which in turn had been affiliated with a clinical trial that used "stem cells ... engineered from the spinal cord of a single fetus electively aborted after eight weeks of gestation. The tissue was obtained with the mothers consent."

"Of course the fetus, from whom the 'tissue' was taken, did not 'give consent,'" LifeNews.com wrote. "So if you give to the ALS Association your money may end up supporting clinical trials that use aborted fetal cells."

Following the report, the Cincinnati Archdiocese warned Catholic school principals not to send donations to the ALS Association, andsome anti-abortion activists have begun making their own "pro-life Ice Bucket Challenge" videos.

CBN News, the Christian TV channel that broadcasts Pat Robertson's 700 Club, put a video of its Ice Bucket Challenge on Facebook, but not without informing its audience that the donations from the challenge would go to "an organization that does not support or use embryonic stem cell research."

Meanwhile, a 2013 FDA-approved study using human stem cells resulted in slowing the progression of ALS to an "extraordinary" degree.

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Anti-Abortion Activists Are Doing Their Own Ice Bucket Challenges

ROCHESTER, Minn. (KTTC) -- Medical officials are talking about a breakthrough clinical trial that could help the heart repair itself.

On Tuesday afternoon, Mayo Clinic and Cardio3 BioSciences officials outlined an FDA-approved clinical trial to be carried out in the United States. A similar trial has already been underway in Europe.

Cardio3 CEO Christian Homsy said stem cells are a major part of this heart-healing process. "What we do is take cells from a patient and we reprogram those cells to become cardiac reparative cells. Those cells have the ability to come and repair the heart." Those stem cells would come from the bone marrow of patients who suffer from heart failure.

This treatment is the result of a Mayo Clinic discovery. In Mayo's breakthrough process, stem cells that are harvested from a cardiac patient's bone marrow undergo a guided treatment designed to improve heart health in people suffering from heart failure.

Cardio3 officials said a manufacturing facility will be the first thing that is needed for this clinical trial, and the rest of the details like staffing will follow.

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Trial to use stem cells to repair heart

Endothelial cells residing in the coronary arteries can function as cardiac stem cells to produce new heart muscle tissue, Vanderbilt University investigators have discovered.

The findings, published recently in Cell Reports, offer insights into how the heart maintains itself and could lead to new strategies for repairing the heart when it fails after a heart attack.

The heart has long been considered to be an organ without regenerative potential, said Antonis Hatzopoulos, Ph.D., associate professor of Medicine and Cell and Developmental Biology.

"People thought that the same heart you had as a young child, you had as an old man or woman as well," he said.

Recent findings, however, have demonstrated that new heart muscle cells are generated at a low rate, suggesting the presence of cardiac stem cells. The source of these cells was unknown.

Hatzopoulos and colleagues postulated that the endothelial cells that line blood vessels might have the potential to generate new heart cells. They knew that endothelial cells give rise to other cell types, including blood cells, during development.

Now, using sophisticated technologies to "track" cells in a mouse model, they have demonstrated that endothelial cells in the coronary arteries generate new cardiac muscle cells in healthy hearts. They found two populations of cardiac stem cells in the coronary arteries -- a quiescent population in the media layer and a proliferative population in the adventitia (outer) layer.

The finding that coronary arteries house a cardiac stem cell "niche" has interesting implications, Hatzopoulos said. Coronary artery disease -- the No. 1 killer in the United States -- would impact this niche.

"Our study suggests that coronary artery disease could lead to heart failure not only by blocking the arteries and causing heart attacks, but also by affecting the way the heart is maintained and regenerated," he said.

The current research follows a previous study in which Hatzopoulos and colleagues demonstrated that after a heart attack, endothelial cells give rise to the fibroblasts that generate scar tissue.

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Coronary arteries hold heart-regenerating cells

PUBLIC RELEASE DATE:

20-Aug-2014

Contact: Craig Boerner craig.boerner@vanderbilt.edu 615-322-4747 Vanderbilt University Medical Center

Endothelial cells residing in the coronary arteries can function as cardiac stem cells to produce new heart muscle tissue, Vanderbilt University investigators have discovered.

The findings, published recently in Cell Reports, offer insights into how the heart maintains itself and could lead to new strategies for repairing the heart when it fails after a heart attack.

The heart has long been considered to be an organ without regenerative potential, said Antonis Hatzopoulos, Ph.D., associate professor of Medicine and Cell and Developmental Biology.

"People thought that the same heart you had as a young child, you had as an old man or woman as well," he said.

Recent findings, however, have demonstrated that new heart muscle cells are generated at a low rate, suggesting the presence of cardiac stem cells. The source of these cells was unknown.

Hatzopoulos and colleagues postulated that the endothelial cells that line blood vessels might have the potential to generate new heart cells. They knew that endothelial cells give rise to other cell types, including blood cells, during development.

Now, using sophisticated technologies to "track" cells in a mouse model, they have demonstrated that endothelial cells in the coronary arteries generate new cardiac muscle cells in healthy hearts. They found two populations of cardiac stem cells in the coronary arteries a quiescent population in the media layer and a proliferative population in the adventitia (outer) layer.

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Vanderbilt researchers find that coronary arteries hold heart-regenerating cells

PUBLIC RELEASE DATE:

19-Aug-2014

Contact: Evgenia Salta Evgenia.Salta@cme.vib-kuleuven.be 32-163-77957 VIB (the Flanders Institute for Biotechnology)

New fundamental knowledge about the regulation of stem cells in the nerve tissue of zebrafish embryos results in surprising insights into neurodegenerative disease processes in the human brain. A new study by scientists at VIB and KU Leuven identifies the molecules responsible for this process.

Zebrafish as a model

The zebrafish is a small fish measuring 3 to 5 cm in length, with dark stripes along the length of its body. They are originally from India, but also a popular aquarium fish. Zebrafish have several unusual characteristics that make them popular for scientific research. Zebrafish eggs are fertilized outside the body, where they develop into embryos. This process occurs very quickly: the most important organs have formed after 24 hours and the young fish have hatched after 3 days. These fish are initially transparent, making them easy to study under the microscope. Zebrafish start reproducing after only 3 months. The genetic code of humans and zebrafish is more than 90 % identical. In addition, the genetic material of these fish is easy to manipulate, meaning that they are often used as a model in the study of all sorts of diseases.

Stem cells in the brain

Evgenia Salta, scientist in the team of Bart De Strooper (VIB KU Leuven), used zebrafish as a model in molecular brain research and discovered a previously unknown regulatory process for the development of nerve cells. Evgenia Salta explains: "The human brain contains stem cells, which are cells that have not matured into nerve cells yet, but do have the potential to do this." Stem cells are of course crucial in the development of the brain. Similar stem cells also exist in zebrafish. Therefore, these fish form an ideal model to study the behavior of these cells. A so-called Notch signaling pathway regulates the further ripening of these cells during early embryonic development. Scientists are still largely in the dark about Notch processes in the brains of Alzheimer patients, but the research by Evgenia Salta is changing this situation.

MicroRNA

The expression of genes, which form the basis of the Notch signaling pathway, is regulated in part by microRNAs (miRNAs), which are short molecules that can inhibit or activate genes. Evgenia Salta: "We specifically studied how miRNA-132 regulates the Notch signaling pathway in stem cells."

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Zebrafish help to unravel Alzheimer's disease

By Estel Grace Masangkay

With help from the zebrafish, a team of Australian researchers has uncovered how hematopoietic stem cells (HSC) renew themselves, considered by many to be the holy grail of stem cell research.

HSCs are a significant type of stem cell present in the blood and bone marrow. These are needed for the replenishment of the bodys supply of blood and immune cells. HSCs already play a part in transplants in patients with blood cancers such as leukemia and myeloma. The stem cells are also studied for their potential to transform into vital cells including muscle, bone, and blood vessels.

Understanding how HSCs form and renew themselves has potential application in the treatment of spinal cord injuries, degenerative disorders, even diabetes. Professor Peter Currie, of the Australian Regenerative Medicine Institute at Victorias Monash University, led a research team to discover a crucial part of HSCs development. Using a high-resolution microscopy, Prof. Curies team caught HSCs on film as they formed inside zebrafish embryos. The discovery was made while the researchers were studying muscle mutations in the aquatic animal.

Zebrafish make HSCs in exactly the same way as humans do, but whats special about these guys is that their embryos and larvae develop free living and not in utero as they do in humans. So not only are these larvae free-swimming, but they are also transparent, so we could see every cell in the body forming, including HSCs, explained Prof. Currie.

While playing the film back, the researchers noticed that a buddy cell came along to help the HSCs form. Called endotome cells, they aided pre-HSCs to turn into HSCs. Prof. Currie said, Endotome cells act like a comfy sofa for pre-HSCs to snuggle into, helping them progress to become fully fledged stem cells. Not only did we identify some of the cells and signals required for HSC formation, we also pinpointed the genes required for endotome formation in the first place.

The next step for the researchers is to locate the signals present in the endotome cells that trigger HSC formation in the embryo. This can help scientists make different blood cells on demand for blood-related disorders. Professor Currie also pointed out the discoverys potential for correcting genetic defects in the cell and transplanting them back in the body to treat disorders.

The teams work was published in the international journal Nature.

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Stem Cell Research Holy Grail' Uncovered, Thanks to Zebrafish