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First Study to Convert Adult Human Cells to Hair-Follicle-Generating Stem Cells has Implications for Hair Regeneration

By LizaAVILA

PHILADELPHIA If the content of many a situation comedy, not to mention late-night TV advertisements, is to be believed, theres an epidemic of balding men, and an intense desire to fix their follicular deficiencies.

One potential approach to reversing hair loss uses stem cells to regenerate the missing or dying hair follicles. But it hasnt been possible to generate sufficient number of hair-follicle-generating stem cells until now.

Xiaowei George Xu, MD, PhD, associate professor of Pathology and Laboratory Medicine and Dermatology at the Perelman School of Medicine, University of Pennsylvania, and colleagues published in Nature Communications a method for converting adult cells into epithelial stem cells (EpSCs), the first time anyone has achieved this in either humans or mice.

The epithelial stem cells, when implanted into immunocompromised mice, regenerated the different cell types of human skin and hair follicles, and even produced structurally recognizable hair shaft, raising the possibility that they may eventually enable hair regeneration in people.

Xu and his team, which includes researchers from Penns departments of Dermatology and Biology, as well as the New Jersey Institute of Technology, started with human skin cells called dermal fibroblasts. By adding three genes, they converted those cells into induced pluripotent stem cells (iPSCs), which have the capability to differentiate into any cell types in the body. They then converted the iPS cells into epithelial stem cells, normally found at the bulge of hair follicles.

Starting with procedures other research teams had previously worked out to convert iPSCs into keratinocytes, Xus team demonstrated that by carefully controlling the timing of the growth factors the cells received, they could force the iPSCs to generate large numbers of epithelial stem cells. In the Xu study, the teams protocol succeeded in turning over 25% of the iPSCs into epithelial stem cells in 18 days. Those cells were then purified using the proteins they expressed on their surfaces.

Comparison of the gene expression patterns of the human iPSC-derived epithelial stem cells with epithelial stem cells obtained from human hair follicles showed that the team had succeeded in producing the cells they set out to make in the first place. When they mixed those cells with mouse follicular inductive dermal cells and grafted them onto the skin of immunodeficient mice, they produced functional human epidermis (the outermost layers of skin cells) and follicles structurally similar to human hair follicles.

This is the first time anyone has made scalable amounts of epithelial stem cells that are capable of generating the epithelial component of hair follicles, Xu says. And those cells have many potential applications, he adds, including wound healing, cosmetics, and hair regeneration.

That said, iPSC-derived epithelial stem cells are not yet ready for use in human subjects, Xu adds. First, a hair follicle contains epithelial cells -- a cell type that lines the bodys vessels and cavities as well as a specific kind of adult stem cell called dermal papillae. Xu and his team mixed iPSC-derived EpSCs and mouse dermal cells to generate hair follicles to achieve the growth of the follicles.

When a person loses hair, they lose both types of cells. Xu explains. We have solved one major problem, the epithelial component of the hair follicle. We need to figure out a way to also make new dermal papillae cells, and no one has figured that part out yet.

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Q&A – Stem cells could offer treatment for a myriad of diseases

By LizaAVILA

Q&A - Stem cells could offer treatment for a myriad of diseases

Tuesday, January 28, 2014

Q.What are stem cells?

Stem cells are different however as they are at an earlier stage in cell development and this means they can make more cells and transform into different cell types such as a skin stem cell can make all the different types of skin cells.

Q. And there are two types? A.Yes. There are two types of stem cells: embryonic stem cells and adult stem cells. Embryonic stem cells can generate all cells of the human body. Adult stem calls generate a more limited number of human cell types.

Q.Why are stem cells so important? A.For many years, adult stem cells have been used to treat rare blood and certain cancers.

However, adult stem cells cant generate all cell types. For example, scientists say there doesnt appear to be an adult stem cell that can make insulin- secreting cells of the pancreas. Embryonic stem cells can, however, as they can generate all cell types and the aim of scientists is to use these embryonic cells to generate healthy tissue to replace cells compromised by disease. This means that embryonic cells are more scientifically useful.

Q. And its also embryonic cells that are the more controversial, right? A.The use of embryonic stem cells is controversial here and in other countries as certain groups believe it is morally wrong to experiment on an embryo that could become a human. Embryonic stem cells are taken from embryos left over after assisted fertility treatments. According to the Irish Stem Cell Foundation, if they werent used for research into human disease, they would be discarded as medical waste. Embryos are not created purely for research purposes they say.

Q. Why are they so useful? A. Among the conditions which scientists believe may eventually be treated by stem cell therapy are Parkinsons disease, Alzheimers disease, heart disease, stroke, arthritis, diabetes, burns and spinal cord damage. Early trials are under way for treating forms of blindness. It is also hoped we can learn from embryonic stem cells how early body tissues develops and more about the pathway of diseases. This will enable us to make better and more effective drugs.

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Converting Adult Human Cells to Hair-Follicle-Generating Stem Cells

By JoanneRUSSELL25

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Newswise PHILADELPHIA - If the content of many a situation comedy, not to mention late-night TV advertisements, is to be believed, theres an epidemic of balding men, and an intense desire to fix their follicular deficiencies.

One potential approach to reversing hair loss uses stem cells to regenerate the missing or dying hair follicles. But it hasnt been possible to generate sufficient number of hair-follicle-generating stem cells until now.

Xiaowei George Xu, MD, PhD, associate professor of Pathology and Laboratory Medicine and Dermatology at the Perelman School of Medicine, University of Pennsylvania, and colleagues published in Nature Communications a method for converting adult cells into epithelial stem cells (EpSCs), the first time anyone has achieved this in either humans or mice.

The epithelial stem cells, when implanted into immunocompromised mice, regenerated the different cell types of human skin and hair follicles, and even produced structurally recognizable hair shaft, raising the possibility that they may eventually enable hair regeneration in people.

Xu and his team, which includes researchers from Penns departments of Dermatology and Biology, as well as the New Jersey Institute of Technology, started with human skin cells called dermal fibroblasts. By adding three genes, they converted those cells into induced pluripotent stem cells (iPSCs), which have the capability to differentiate into any cell types in the body. They then converted the iPS cells into epithelial stem cells, normally found at the bulge of hair follicles.

Starting with procedures other research teams had previously worked out to convert iPSCs into keratinocytes, Xus team demonstrated that by carefully controlling the timing of the growth factors the cells received, they could force the iPSCs to generate large numbers of epithelial stem cells. In the Xu study, the teams protocol succeeded in turning over 25% of the iPSCs into epithelial stem cells in 18 days. Those cells were then purified using the proteins they expressed on their surfaces.

Comparison of the gene expression patterns of the human iPSC-derived epithelial stem cells with epithelial stem cells obtained from human hair follicles showed that the team had succeeded in producing the cells they set out to make in the first place. When they mixed those cells with mouse follicular inductive dermal cells and grafted them onto the skin of immunodeficient mice, they produced functional human epidermis (the outermost layers of skin cells) and follicles structurally similar to human hair follicles.

This is the first time anyone has made scalable amounts of epithelial stem cells that are capable of generating the epithelial component of hair follicles, Xu says. And those cells have many potential applications, he adds, including wound healing, cosmetics, and hair regeneration.

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Are Stem Cells The Cure To Baldness?

By raymumme

January 28, 2014

Brett Smith for redOrbit.com Your Universe Online

While a Chinese cream may not have cured George Costanzas baldness in a classic Seinfeld episode, stem cell research from scientists at the University of Pennsylvania has shown the potential for regenerating hair follicles which could lead to relief for hair-challenged men everywhere.

According to a new report published in the journal Nature Communications, the Pennsylvania researchers have developed a groundbreaking method for converting adult cells into epithelial stem cells (EpSCs). Similar previous efforts have failed to generate an adequate number of hair-follicle-generating stem cells.

In the study, epithelial stem cells were inserted into immunocompromised mice. The stem cells regenerated the various cell types for human skin and hair follicles, and provided structurally identifiable hair shafts, raising the possibility of hair regeneration in humans.

The study team began with human skin cells referred to as dermal fibroblasts. By incorporating three genes, they modified those cells into induced pluripotent stem cells (iPSCs), which have the capacity to differentiate into any cell types in the human body. Next, they modified the iPS cells into epithelial stem cells, commonly located at the base of hair follicles.

Starting with procedures other research groups had worked out to transfer iPSCs into skin cells, Xus team figured out that by carefully manipulating the timing of the cell growth factors, they could drive the iPSCs to produce large quantities of epithelial stem cells. This method was able to turn more than 25 percent of the iPSCs into epithelial stem cells within 18 days. Those cells were then purified based on the proteins they showed on their surfaces.

Comparison of the engineered cells with epithelial stem tissue obtained from hair follicles revealed the team succeeded in making the cells they set out to produce. After mixing all those cells with mouse follicular inductive dermal cells and attaching them onto the pores and skin of immunodeficient mice, the team was able to produce efficient outer layers of human skin tissue and follicles structurally similar to those generated by human hair.

This is the first time anyone has made scalable amounts of epithelial stem cells that are capable of generating the epithelial component of hair follicles, said study author Dr. Xiaowei George Xu, associate professor of pathology and laboratory medicine and dermatology at the university. He added that these cells could be used for healing, cosmetics and hair regeneration.

Xu cautioned that iPSC-derived epithelial stem cells are not yet ready for human subjects.

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Baldness Cure May Have Inched a Bit Closer

By daniellenierenberg

Posted: Tuesday, January 28, 2014, 9:00 AM

TUESDAY, Jan. 28, 2014 (HealthDay News) -- Scientists might be able to offer "hair-challenged" males a new glimmer of hope when it comes to reversing baldness.

Researchers from the University of Pennsylvania say they've gotten closer to being able to use stem cells to treat thinning hair -- at least in mice.

The researchers said that although using stem cells to regenerate missing or dying hair follicles is considered a potential way to reverse hair loss, it hasn't been possible to create adequate numbers of hair-follicle-generating stem cells -- specifically cells of the epithelium, the name for tissues covering the surface of the body.

But new findings indicate that this may now be achievable.

"This is the first time anyone has made scalable amounts of epithelial stem cells that are capable of generating the epithelial component of hair follicles," Dr. Xiaowei Xu, an associate professor of dermatology at Penn's Perelman School of Medicine, said in a university news release.

Those cells have many potential applications that extend to wound healing, cosmetics and hair regeneration, Xu said.

In the new study, Xu's team converted induced pluripotent stem cells (iPSCs) -- reprogrammed adult stem cells with many of the characteristics of embryonic stem cells -- into epithelial stem cells. This is the first time this has been done in either mice or people, the researchers said.

The epithelial stem cells were mixed with certain other cells and implanted into mice. They produced the outermost layers of skin cells and follicles that are similar to human hair follicles, according to the study, which was published Jan. 28 in the journal Nature Communications. This suggests that these cells might eventually help regenerate hair in people, the researchers said.

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Baldness Cure May Have Inched a Bit Closer

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:: 28, Jan 2014 :: SINGAPORE SCIENTISTS SUCCEED IN MANIPULATING STEM CELLS INTO LIVER AND PANCREAS PRECURSOR CELLS

By raymumme

28 January 2014-Scientists from the Genome Institute of Singapore (GIS) in A*STAR have developed a novel method of directing human pluripotent stem cells (hPSCs) into highly pure populations of endoderm[1], a valuable cell type that gives rise to organs including the liver and pancreas.

These cells are highly sought-after for therapeutic and biotechnological purposes, but have been historically difficult to attain from hPSCs. The ability to generate pure endoderm at higher yields from hPSCs is a key and important step towards the use of stem cells in clinical applications.

The discovery, published in the prestigious scientific journal Cell Stem Cell in January 2014, was led by Dr Bing Lim, Senior Group Leader and Associate Director of Cancer Stem Cell Biology at the GIS, Dr Lay Teng Ang, a postdoctoral fellow from Dr Lims lab, and Kyle Loh, a graduate student at Stanford University School of Medicine.

hPSCs are stem cells that can generate over 200 distinct cell types in the human body. They respond to multiple external protein instructions to differentiate into other cell types. Therefore, generating one single cell type from hPSCs, and a pure population of that given cell type, is delicate as hPSCs have a tendency to also form other types of cells.

Employing a highly systematic and novel approach, the group screened for proteins and chemicals that promote the formation of a single desired cell type, and concurrently block induction of unwanted cell types. This strategy uncovered a combination of triggers that could drive hPSCs towards pure populations of endoderm. The valuable cells produced and the insights gained from this work have brought stem cells one step closer to clinical translation and furthered basic research into the understanding of how cell fates are specified during stem cell differentiation.

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Failure to legislate ‘will hurt research’

By LizaAVILA

Failure to legislate will hurt research

Tuesday, January 28, 2014

Even though stem cell manufacture has just been licensed in this country, the Governments ongoing failure to legislate in this area means pharmaceutical giants will still be wary of investing here, according to an expert in stem cell therapy.

CCMI General Manager Andrew Finnerty, CCMI Director Tim O'Brien, Minister Sean Sherlock and President of NUI Galway Dr. James Browne. Photograph by Aengus McMahon

Once the stem cells are harvested from the bone marrow of adult donors, they are grown in the Galway laboratory to generate sufficient quantities.

The first clinical trial using these stem cells is being funded by the Health Research Board and Science Foundation Ireland and will investigate the safety of using mesenchymal stem cells (MSCs) isolated from bone marrow for the treatment of critical limb ischemia, a complication associated with diabetes which can lead to limb amputation.

John ODea of the Irish Medical Devices Association (IMDA) said the centre was a key step.

I look forward to seeing its continued growth to assist in developing the skill sets and techniques that will be needed to embrace the new manufacturing opportunities that this exciting area will bring, he said.

The centre, one of a handful in Europe authorised for stem cell manufacture, has been developed by researchers at NUIGs regenerative medicine institute.

However, Dr Stephen Sullivan, chief scientific officer with the Irish Stem Cell Foundation warned all stem cell research operates at a pan-global level driven by big pharma and international equity firms and these players will only engage with researchers in countries where there is solid stem cell legislation in place. He welcomed the centre as a first step but said if Ireland is to compete at a top international standard, legislation remains necessary.

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Stem cells lab to open in Galway

By Dr. Matthew Watson

Published Monday, 27 January 2014

A young teenager with diabetes tests his blood levels. (UTV)

Scientists behind the new facility at the National University of Ireland Galway will aim to produce adult cells to combat conditions like diabetes, arthritis and heart disease.

Stem cells created at the lab will be used in clinical trials following regulatory approval - the first of which is to test their effects on critical limb ischemia, a common complication associated with diabetes which often results in amputation.

The cells, mesenchymal stem cells (MSCs), will undergo safety tests after being isolated from bone marrow from donors and grown in the laboratory to generate sufficient quantities.

The university said it will position it as a global player in regenerative medicine.

NUI Galway's Centre for Cell Manufacturing Ireland is the first facility on the island of Ireland to receive a licence from the Irish Medicines Board to manufacture culture-expanded stem cells for human use.

It is one of less than half a dozen in Europe authorised for the process.

Some 70% of pharmaceutical companies have regenerative medicine therapies in development, with 575 active trials in cell and gene therapy under way.

There are more than 1,900 cell therapy clinical trials ongoing worldwide with regenerative medicine products generating more than $1bn in revenue in 2012.

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Stem cells lab to open in Galway

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Ireland university lab in stem cells move

By NEVAGiles23

AAP Scientists in Ireland aim to produce adult cells to combat conditions like arthritis.

Stem cells for human use are to be made in a university lab in the first medical program of its kind in Ireland.

Scientists behind the new facility at the National University of Ireland (NUI) Galway will aim to produce adult cells to combat conditions like arthritis, heart disease and diabetes.

Stem cells created at the lab will be used in clinical trials following regulatory approval - the first of which is to test their effects on critical limb ischemia, a common complication associated with diabetes which often results in amputation.

The cells, mesenchymal stem cells (MSCs), will undergo safety tests after being isolated from bone marrow from donors and grown in the laboratory to generate sufficient quantities.

The university said it will position it as a global player in regenerative medicine.

NUI Galway's Centre for Cell Manufacturing Ireland is the first facility in Ireland to receive a licence from the Irish Medicines Board to manufacture culture-expanded stem cells for human use.

And it is one of less than half a dozen in Europe authorised for the process.

"Developing Galway's role as med-tech hub of global standing, the Centre for Cell Manufacturing Ireland captures NUI Galway's commitment to bring bold ideas to life," said NUI Galway president Dr Jim Browne.

"Innovation can bridge the gap between patient and provider and meet the needs of industry and the wider society in a balanced way."

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New mechanism for genome unpacking in stem cells

By raymumme

11 hours ago by Katarina Sternudd

Scientists at Karolinska Institutet and Gurdon Institute in Cambridge, United Kingdom have identified a novel mechanism that allows pluripotent stem cells to maintain their genome in an unpacked state, and thereby maintain their unique property to give raise to all types of specialized cells in the body. The findings are presented in the journal Nature.

Embryonic stem cells and induced pluripotent stem cells have the capacity to give rise to all cell types present in the adult body. To maintain this immature state, genes that are turned on in specialized cells must remain inactive in pluripotent cells, but ready to be quickly activated upon maturation into, for example, a cell in the skin or liver. The genome of a cell is packed in the nucleus, in a structure called chromatin. If the chromatin packing is tight (condensed), activatory molecules cannot access parts of the genome that control the activation of genes. Thus, for a certain gene to be activated, the chromatin structure must be unpacked (decondensation).

Pluripotent stem cells are unique in that their genome is partially unpacked (chromatin decondensation), when compared to specialized cells, to allow rapid activation of differentiation genes upon a given stimuli. In this published study, an international team, lead by Professor Tony Kouzarides, at the Gurdon Institute, University of Cambridge, identified a specific enzymatic activity, called citrullination, that contributes to decondensed chromatin state in pluripotent cells.

"The genome (DNA) is highly negatively charged and is associated in the chromatin structure with proteins called histones, which are highly positively charged. We found that in pluripotent cells, citrullination reduces the charge of some histones, weakening their association with the genome and contributing to decondensation", says Gonalo Castelo-Branco, principal investigator at Karolinska Institutet and co-first author in the study with Maria Christophorou of the Gurdon Institute.

Gonalo Castelo-Branco's research group at Karolinska Institutet is now investigating roles for citrullination in other immature cells, such as oligodendrocyte precursors in the brain, which participate in myelin regeneration in multiple sclerosis, MS.

Research in this study was funded by grants from Cancer Research UK, the Swedish Research Council, EMBO, European Union 7th Framework Programme (FP7) Marie Curie Actions, among others grants. Gonalo Castelo-Branco implemented parts of the study at the Gurdon Institute, where he was previously a researcher, and at Karolinska Institutet. Among the study authors is also professor John Gurdon, laureate of the Nobel Prize in Physiology or Medicine 2012. Apart from Sweden and United Kingdom, scientists from Denmark, Brasil and USA participated in the study.

Explore further: New method increases supply of embryonic stem cells

More information: "Citrullination regulates pluripotency and histone H1 binding to chromatin." Maria A. Christophorou, Gonalo Castelo-Branco, Richard P. Halley-Stott, et al. Nature (2014) DOI: 10.1038/nature12942. Received 06 September 2012 Accepted 06 December 2013 Published online 26 January 2014

Journal reference: Nature

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Ireland’s first stem cell manufacturing centre approved at NUI Galway

By LizaAVILA

Embryonic stem cells have been highly valued for their ability to turn into any type of cell in the body.

Stem cells can be manufactured for human use for the first time in Ireland, following Irish Medicines Board licensing of a new facility in Galway.

NUI Galways Centre for Cell Manufacturing Ireland aims to culture adult stem cells to tackle conditions such as arthritis, heart disease, diabetes and associated conditions.

The centre, which is one of less than half a dozen in Europe authorised for stem cell manufacture, has been developed by researchers at NUIGs regenerative medicine institute.

Stem cells serve as the bodys repair mechanism. They can be isolated from tissues such as bone marrow and fat, and cultured in laboratory settings.

More controversially, embryonic stem cells have been highly valued for their ability to turn into any type of cell in the body, but scientists can now use reprogrammed adult skin cells to create a stem cell that is very similar to embryonic versions.

The centre will be opened today by Minister of State for Research and Innovation Sen Sherlock, at a time when the Health Research Board and Science Foundation Ireland have approved funding there for clinical trials on using mesenchymal stem cells cells that can differentiate into a variety of types for treatment of critical limb ischemia, a condition associated with diabetes that can result in amputation.

The new centres director Prof Tim OBrien explained that the stem cells must be grown in the laboratory to generate sufficient quantities, following their isolation from the bone marrow of adult donors, and the facility will help Ireland to develop therapies for a broad range of clinical problems which do not have effective treatments today.

It will also allow us to translate discoveries from the basic stem cell research programme led by Prof Frank Barry at the Science Foundation Ireland-funded REMEDI to the clinic, and to be competitive for grant funding under the Horizon 2020 programme of the EU, he said.

Stem cell research in Ireland is in what scientists have described as a legislative lacuna, but this relates to use of embryonic stem cells and does not in any way inhibit the use of adult stem cells, Prof OBrien explained.

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Island’s first stem cell manufacturing centre approved at NUI Galway

By NEVAGiles23

Embryonic stem cells have been highly valued for their ability to turn into any type of cell in the body.

Stem cells can be manufactured for human use for the first time in Ireland, following Irish Medicines Board licensing of a new facility in Galway.

NUI Galways Centre for Cell Manufacturing Ireland aims to culture adult stem cells to tackle conditions such as arthritis, heart disease, diabetes and associated conditions.

The centre, which is one of less than half a dozen in Europe authorised for stem cell manufacture, has been developed by researchers at NUIGs regenerative medicine institute.

Stem cells serve as the bodys repair mechanism. They can be isolated from tissues such as bone marrow and fat, and cultured in laboratory settings.

More controversially, embryonic stem cells have been highly valued for their ability to turn into any type of cell in the body, but scientists can now use reprogrammed adult skin cells to create a stem cell that is very similar to embryonic versions.

The centre will be opened today by Minister of State for Research and Innovation Sen Sherlock, at a time when the Health Research Board and Science Foundation Ireland have approved funding there for clinical trials on using mesenchymal stem cells cells that can differentiate into a variety of types for treatment of critical limb ischemia, a condition associated with diabetes that can result in amputation.

The new centres director Prof Tim OBrien explained that the stem cells must be grown in the laboratory to generate sufficient quantities, following their isolation from the bone marrow of adult donors, and the facility will help Ireland to develop therapies for a broad range of clinical problems which do not have effective treatments today.

It will also allow us to translate discoveries from the basic stem cell research programme led by Prof Frank Barry at the Science Foundation Ireland-funded REMEDI to the clinic, and to be competitive for grant funding under the Horizon 2020 programme of the EU, he said.

Stem cell research in Ireland is in what scientists have described as a legislative lacuna, but this relates to use of embryonic stem cells and does not in any way inhibit the use of adult stem cells, Prof OBrien explained.

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Clinical trial studies vaccine targeting cancer stem cells in brain cancers

By JoanneRUSSELL25

An early-phase clinical trial of an experimental vaccine that targets cancer stem cells in patients with recurrent glioblastoma multiforme, the most common and aggressive malignant brain tumor, has been launched by researchers at Cedars-Sinai's Department of Neurosurgery, Johnnie L. Cochran, Jr. Brain Tumor Center and Department of Neurology.

Like normal stem cells, cancer stem cells have the ability to self-renew and generate new cells, but instead of producing healthy cells, they create cancer cells. In theory, if the cancer stem cells can be destroyed, a tumor may not be able to sustain itself, but if the cancer originators are not removed or destroyed, a tumor will continue to return despite the use of existing cancer-killing therapies.

The Phase I study, which will enroll about 45 patients and last two years, evaluates safety and dosing of a vaccine created individually for each participant and designed to boost the immune system's natural ability to protect the body against foreign invaders called antigens. The drug targets a protein, CD133, found on cancer stem cells of some brain tumors and other cancers.

Immune system cells called dendritic cells will be derived from each patient's blood, combined with commercially prepared glioblastoma proteins and grown in the laboratory before being injected under the skin as a vaccine weekly for four weeks and then once every two months, according to Jeremy Rudnick, MD, neuro-oncologist in the Cedars-Sinai Department of Neurosurgery and Department of Neurology, the study's principal investigator.

Dendritic cells are the immune system's most powerful antigen-presenting cells -- those responsible for helping the immune system recognize invaders. By being loaded with specific protein fragments of CD133, the dendritic cells become "trained" to recognize the antigen as a target and stimulate an immune response when they come in contact.

The cancer stem cell study is the latest evolution in Cedars-Sinai's history of dendritic cell vaccine research, which was introduced experimentally in patient trials in 1998.

Cedars-Sinai's brain cancer stem cell study is open to patients whose glioblastoma multiforme has returned following surgical removal. Potential participants will be screened for eligibility requirements and undergo evaluations and medical tests at regular intervals. The vaccine and study-related tests and follow-up care will be provided at no cost to patients. For more information, call 1-800-CEDARS-1 or contact Cherry Sanchez by phone at 310-423-8100 or email cherry.sanchez@cshs.org.

Story Source:

The above story is based on materials provided by Cedars-Sinai Medical Center. Note: Materials may be edited for content and length.

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Abandoned dog receives historic stem cell therapy – Video

By JoanneRUSSELL25


Abandoned dog receives historic stem cell therapy
Veterinarians across the country now have a way to improve the lives of their patients by using a tool to combat osteoarthritis. On Thursday, one dog made hi...

By: UpNorthLive

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Stem-cell therapy restores faith for arthritic pets

By Dr. Matthew Watson

ELLSWORTH Visitors to the Bellaire pet crisis center With a Little help From My Friends get an official welcome from Moka.

The Labrador retriever was found behind a Bellaire restaurant in 2011 and now serves as the centers mascot.

Peforming her duties has been increasingly difficult for the dog, who suffers from severe arthritis in her hips. So recently the center turned to Ellsworth veterinarian Christian Randall of North Country Veterinary Services, the first in northern Michigan to offer in-clinic adipose stem cell therapy.

The procedure uses a pets own blood and tissue to produce plasma-rich platelets and stem cells that proliferate growth in damaged areas.

Dormant stem cells are separated from adipose -- fat tissue -- and activated with an LED technology that uses three different wave lengths of light. Then the cells are injected directly into the affected area or administered intravenously to help promote regeneration. The result is a decrease in pain and lameness and increased range of motion.

Its using the bodys own repair cells to repair damage, said Trey Smith, director of laboratory services for MediVet America, which developed the technology Randall uses.

The therapy is the first treatment to help heal and slow the progression of osteoarthritis and degenerative joint disease rather than just cope with the symptoms, said Randall, who saw the results while studying at Virginia Equine Imaging and now plans to use it on equine as well as canine and feline patients.

It concentrates, speeds up and amplifies the bodys own healing power, he said.

Stem cell therapy has been around for a while, but in-clinic availability of the technology is new. Only a handful of veterinarians in Ann Arbor and Grand Rapids offer the services, said Randall, who charges $1,800 to treat a dog or cat. Repeat injections are possible with banked plasma-rich platelets and stem cells.

Before the one-day procedure, veterinarians had to send blood and tissue to an outside lab for processing, a more costly three-day procedure that requires an animal's return visit to the vet for injection.

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New trial offers new hope for those with spinal cord injuries

By NEVAGiles23

CALGARY- A Winnipeg paramedic has become the first Canadian to take part in an international clinical trial involving the treatment of spinal cord injuries using stem cells.

Alex Petric was injured last year during a winter vacation in Panama.

I misjudged the water and just dove in, the 29-year-old recalls. I hit shallow water and became paralyzed immediately.

Petric, now a paraplegic, became involved with the trial just four months after his injury.

Its a phase one trial which means that its looking at the safety and tolerability of the procedure, explains Dr. Steve Casha, medical team lead for the University of Calgary.

A Swiss company, calledStem Cells Incorporatedis the driving force behind the research. A team in Switzerland has already treated eight other spinal cord patients.

During the trial, researchers must first identify the precise location of Petrics spinal cord injury. Then, stem cells are injected into two sites above and two sites below the injury to hopefully recreate lost tissue.

What these cells will hopefully do, and what they seem to do from previous clinical studies is take up residence in the spinal cord. They are a self-renewing population and they can differentiate or become various cells, Dr. Casha explains.

While the first phase of the trial focuses on safety, the ultimate goal is to develop a cure for spinal cord injuries. So far, two patients in the study have regained sensation.

Petric says his expectations are realistic, but his dream is to walk again.

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New trial offers new hope for those with spinal cord injuries

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Cedars-Sinai clinical trial studies vaccine targeting cancer stem cells in brain cancers

By Dr. Matthew Watson

PUBLIC RELEASE DATE:

24-Jan-2014

Contact: Sandy Van sandy@prpacific.com 808-526-1708 Cedars-Sinai Medical Center

LOS ANGELES (Jan. 24, 2014) An early-phase clinical trial of an experimental vaccine that targets cancer stem cells in patients with recurrent glioblastoma multiforme, the most common and aggressive malignant brain tumor, has been launched by researchers at Cedars-Sinai's Department of Neurosurgery, Johnnie L. Cochran, Jr. Brain Tumor Center and Department of Neurology.

Like normal stem cells, cancer stem cells have the ability to self-renew and generate new cells, but instead of producing healthy cells, they create cancer cells. In theory, if the cancer stem cells can be destroyed, a tumor may not be able to sustain itself, but if the cancer originators are not removed or destroyed, a tumor will continue to return despite the use of existing cancer-killing therapies.

The Phase I study, which will enroll about 45 patients and last two years, evaluates safety and dosing of a vaccine created individually for each participant and designed to boost the immune system's natural ability to protect the body against foreign invaders called antigens. The drug targets a protein, CD133, found on cancer stem cells of some brain tumors and other cancers.

Immune system cells called dendritic cells will be derived from each patient's blood, combined with commercially prepared glioblastoma proteins and grown in the laboratory before being injected under the skin as a vaccine weekly for four weeks and then once every two months, according to Jeremy Rudnick, MD, neuro-oncologist in the Cedars-Sinai Department of Neurosurgery and Department of Neurology, the study's principal investigator.

Dendritic cells are the immune system's most powerful antigen-presenting cells those responsible for helping the immune system recognize invaders. By being loaded with specific protein fragments of CD133, the dendritic cells become "trained" to recognize the antigen as a target and stimulate an immune response when they come in contact.

The cancer stem cell study is the latest evolution in Cedars-Sinai's history of dendritic cell vaccine research, which was introduced experimentally in patient trials in 1998.

Cedars-Sinai's brain cancer stem cell study is open to patients whose glioblastoma multiforme has returned following surgical removal. Potential participants will be screened for eligibility requirements and undergo evaluations and medical tests at regular intervals. The vaccine and study-related tests and follow-up care will be provided at no cost to patients. For more information, call 1-800-CEDARS-1 or contact Cherry Sanchez by phone at 310-423-8100 or email cherry.sanchez@cshs.org.

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Cedars-Sinai clinical trial studies vaccine targeting cancer stem cells in brain cancers

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Tracing unique cells with mathematics

By raymumme

Jan. 23, 2014 Stem cells can turn into heart cells, skin cells can mutate to cancer cells; even cells of the same tissue type exhibit small heterogeneities. Scientists use single-cell analyses to investigate these heterogeneities. But the method is still laborious and considerable inaccuracies conceal smaller effects. Scientists at the Helmholtz Zentrum Muenchen, at the Technische Unitversitaet Muenchen and the University of Virginia (USA) have now found a way to simplify and improve the analysis by mathematical methods.

Each cell in our body is unique. Even cells of the same tissue type that look identical under the microscope differ slightly from each other. To understand how a heart cell can develop from a stem cell, why one beta-cell produces insulin and the other does not, or why a normal tissue cell suddenly mutates to a cancer cell, scientists have been targeting the activities of ribonucleic acid, RNA.

Proteins are constantly being assembled and disassembled in the cell. RNA molecules read blueprints for proteins from the DNA and initiate their production. In the last few years scientists around the world have developed sequencing methods that are capable of detecting all active RNA molecules within a single cell at a certain time.

At the end of December 2013 the journal Nature Methods declared single-cell sequencing the "Method of the Year." However, analysis of individual cells is extremely complex, and the handling of the cells generates errors and inaccuracies. Smaller differences in gene regulation can be overwhelmed by the statistical "noise."

Scientists led by Professor Fabian Theis, Chair of Mathematical modeling of biological systems at the Technische Universitaet Muenchen and director of the Institute of Computational Biology at the Helmholtz Zentrum Muenchen, have now found a way to considerably improve single-cell analysis by applying methods of mathematical statistics.

Instead of just one cell, they took 16-80 samples with ten cells each. "A sample of ten cells is much easier to handle," says Professor Theis. "With ten times the amount of cell material, the influences of ambient conditions can be markedly suppressed." However, cells with different properties are then distributed randomly on the samples. Therefore Theis's collaborator Christiane Fuchs developed statistical methods to still identify the single-cell properties in the mixture of signals.

On the basis of known biological data, Theis and Fuchs modeled the distribution for the case of genes that exhibit two well-defined regulatory states. Together with biologists Kevin Janes and Sameer Bajikar at the University of Virginia in Charlottesville (USA), they were able to prove experimentally that with the help of statistical methods samples containing ten cells deliver results of higher accuracy than can be achieved through analysis of the same number of single cell samples.

In many cases, several gene actions are triggered by the same factor. Even in such cases, the statistical method can be applied successfully. Fluorescent markers indicate the gene activities. The result is a mosaic, which again can be checked to spot whether different cells respond differently to the factor.

The method is so sensitive that it even shows one deviation in 40 otherwise identical cells. The fact that this difference actually is an effect and not a random outlier could be proven experimentally.

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Statistical Methods Improve Biological Single-Cell Analyses

By JoanneRUSSELL25

Stem cells can turn into heart cells, skin cells can mutate to cancer cells; even cells of the same tissue type exhibit small heterogeneities. Scientists use single-cell analyses to investigate these heterogeneities. But the method is still laborious and considerable inaccuracies conceal smaller effects. Scientists at the Technische Universitaet Muenchen (TUM), the Helmholtz Zentrum Muenchen and the University of Virginia (USA) have now found a way to simplify and improve the analysis by mathematical methods.

Each cell in our body is unique. Even cells of the same tissue type that look identical under the microscope differ slightly from each other. To understand how a heart cell can develop from a stem cell, why one beta-cell produces insulin and the other does not, or why a normal tissue cell suddenly mutates to a cancer cell, scientists have been targeting the activities of ribonucleic acid, RNA.

Proteins are constantly being assembled and disassembled in the cell. RNA molecules read blueprints for proteins from the DNA and initiate their production. In the last few years scientists around the world have developed sequencing methods that are capable of detecting all active RNA molecules within a single cell at a certain time.

At the end of December 2013 the journal Nature Methods declared single-cell sequencing the "Method of the Year." However, analysis of individual cells is extremely complex, and the handling of the cells generates errors and inaccuracies. Smaller differences in gene regulation can be overwhelmed by the statistical "noise."

Easier And More Accurate, Thanks To Statistics

Scientists led by Professor Fabian Theis, Chair of Mathematical modeling of biological systems at the Technische Universitaet Muenchen and director of the Institute of Computational Biology at the Helmholtz Zentrum Muenchen, have now found a way to considerably improve single-cell analysis by applying methods of mathematical statistics.

Instead of just one cell, they took 16-80 samples with ten cells each. "A sample of ten cells is much easier to handle," says Professor Theis. "With ten times the amount of cell material, the influences of ambient conditions can be markedly suppressed." However, cells with different properties are then distributed randomly on the samples. Therefore Theis's collaborator Christiane Fuchs developed statistical methods to still identify the single-cell properties in the mixture of signals.

Combining Model and Experiment

On the basis of known biological data, Theis and Fuchs modeled the distribution for the case of genes that exhibit two well-defined regulatory states. Together with biologists Kevin Janes and Sameer Bajikar at the University of Virginia in Charlottesville (USA), they were able to prove experimentally that with the help of statistical methods samples containing ten cells deliver results of higher accuracy than can be achieved through analysis of the same number of single cell samples.

In many cases, several gene actions are triggered by the same factor. Even in such cases, the statistical method can be applied successfully. Fluorescent markers indicate the gene activities. The result is a mosaic, which again can be checked to spot whether different cells respond differently to the factor.

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Insulin-producing beta cells from stem cells

By Dr. Matthew Watson

Jan. 23, 2014 The Wnt/-catenin signaling pathway and microRNA 335 are instrumental in helping form differentiated progenitor cells from stem cells. These are organized in germ layers and are thus the origin of different tissue types, including the pancreas and its insulin-producing beta cells. With these findings, Helmholtz Zentrum Mnchen scientists have discovered key molecular functions of stem cell differentiation which could be used for beta cell replacement therapy in diabetes. The results of the two studies were published in the journal Development.

The findings of the scientists of the Institute of Diabetes and Regeneration Research (IDR) at Helmholtz Zentrum Mnchen (HMGU) provide new insights into the molecular regulation of stem cell differentiation. These results reveal important target structures for regenerative therapy approaches to chronic diseases such as diabetes.

During embryonic development, organ-specific cell types are formed from pluripotent stem cells, which can differentiate into all cell types of the human body. The pluripotent cells of the embryo organize themselves at an early stage in germ layers: the endoderm, mesoderm and ectoderm. From these three cell populations different functional tissue cells arise, such as skin cells, muscle cells, and specific organ cells.

Various signaling pathways are important for this germ layer organization, including the Wnt/-catenin signaling pathway. The cells of the pancreas, such as the beta cells, originate from the endoderm, the germ layer from which the gastrointestinal tract, the liver and the lungs also arise. Professor Heiko Lickert, director of the IDR, in collaboration with Professor Gunnar Schotta of LMU Mnchen, showed that the Wnt/-catenin signaling pathway regulates Sox17, which in turn regulates molecular programs that assign pluripotent cells to the endoderm, thus inducing an initial differentiation of the stem cells. In another project Professor Lickert and his colleague Professor Fabian Theis, director of the Institute of Computational Biology (ICB) at Helmholtz Zentrum Mnchen, discovered an additional mechanism that influences the progenitor cells. miRNA-335, a messenger nucleic acid, regulates the endodermal transcription factors Sox17 and Foxa2 and is essential for the differentiation of cells within this germ layer and their demarcation from the adjacent mesoderm. The concentrations of the transcription factors determine here whether these cells develop into lung, liver or pancreas cells. To achieve these results, the scientists combined their expertise in experimental research with mathematical modeling.

"Our findings represent two key processes of stem cell differentiation," said Lickert. "With an improved understanding of cell formation we can succeed in generating functional specialized cells from stem cells. These could be used for a variety of therapeutic approaches. In diabetes, we may be able to replace the defective beta cells, but regenerative medicine also offers new therapeutic options for other organ defects and diseases."

Diabetes is characterized by a dysfunction of the insulin-producing beta cells of the pancreas. Regenerative treatment approaches aim to renew or replace these cells. An EU-funded research project ('HumEn'), in which Lickert and his team are participating, shall provide further insights in the field of beta-cell replacement therapy.

The aim of research at Helmholtz Zentrum Mnchen, a partner in the German Center for Diabetes Research (DZD), is to develop new approaches for the diagnosis, treatment and prevention of major common diseases such as diabetes mellitus.

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Insulin-producing beta cells from stem cells

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