Could the cure for baldness be found within our own skin?

For the first time, researchers from the Perelman School of Medicine at the University of Pennsylvania were successfully able to take human skin cells and transform them into hair-follicle-generating stem cells. These cells were then transplanted onto mice, and turned into human-like skin and hair follicles. The mice eventually grew tiny hair shafts.

The study was published Jan. 28 in Nature Communications.

The researchers began by using a type of skin cell known as dermal fibroblasts. They added three genes in order to transform them into induced pluripotent stem cells (iPSCs). These stem cells have the ability to transform into other cells found throughout the body.

Specifically, the iPSCs in this study were made into epithelial cells, which make up connective, muscle and nerve tissue. These cells are normally found at the bulb-like ends of hair follicles. The team was able to accomplish this by controlling the cells' growth time, and were able to turn 25 percent of the iPSCs into epithelial stem cells in about 18 days.

The epithelial stem cells were then mixed with mice hair follicle skin cells. They were then transplanted onto mice who had their immune systems suppressed. The cells produced human outer skin layer cells and follicles that were close to actual human hair follicles, which then grew the beginning of the hair shafts.

Dr. Xiaowei George Xu, associate professor of pathology, laboratory medicine and dermatology at the Perelman School of Medicine, said in a press release that these cells may be able to do more than generate hair. They could also be used in wound care and in cosmetics.

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 explained.

But, the research is still far from practical use. The next step is to create the other type of cell found in hair, dermal papillae, which are small bumps of cells found in the second layer of skin that poke into the top layer of skin. These dermal papillae create our fingerprints, among other things. For the experiments, the researchers used mice cells to make up for the lack of human ones.

When a person loses hair, they lose both types of cells, Xu said. 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.

Read more from the original source:
Bye bye baldness? Researchers regrow hair using skin cells

Carving out a Niche for Stem Cells
Carving out a Niche for Stem Cells Air date: Wednesday, January 15, 2014, 3:00:00 PM Runtime: 01:04:50 Description: Wednesday Afternoon Lecture Series Typica...

By: nihvcast

More:
Carving out a Niche for Stem Cells - Video

Scientists have created embryonic-like stem cells by simply bathing ordinary skin or blood cells in a weak acid solution for half an hour in an astonishing breakthrough that could allow doctors in the future to repair diseased tissue with a patient's own cells.

Researchers at the Riken Centre for Developmental Biology in Japan have announced the breakthrough in the journal Nature and it has been welcomed in Britain as an important step towards using stem cells routinely in medicine without the ethical or practical problems of creating human embryos or genetically modified cells.

Although the research was carried out on laboratory mice, scientists believe that the same approach should also work on human cells. It radically changes the way "pluripotent" stem cells - which can develop into any of the specialised tissues of the body - can be created from a patient's own cells as part of a "self-repair" kit.

"Once again Japanese scientists have unexpectedly rewritten the rules on making pluripotent cells from adult cells....that requires only transient exposure of adult cells to an acidic solution. How much easier can it possibly get?" said Professor Chris Mason, chair of regenerative medicine at University College London.

Two studies in Nature have shown that there is now a third way of producing pluripotent stem cells, other than creating embryos or inducing the changes by introducing new genes into a cell. The third way is by far the simplest of the three approaches, scientists said.

The scientists believe that the acidity of the solution created a "shock" that caused the blood cells of adult mice to revert to their original, embryonic-like state. From this pluripotent state, the newly created stem cells were cultured in specially prepared solutions of growth factors to develop into fully mature cells, including an entire foetus.

Professor Robin Lovell-Badge of the Medical Research Council's National Institute for Medical Research, said: "It is going to be a while before the nature of these cells are understood, and whether they might prove to be useful for developing therapies, but the really intriguing thing to discover will be the mechanism underlying how a low pH shock triggers reprogramming. And why it does not happen when we eat lemon or vinegar or drink cola?"

See more here:
Groundbreaking discovery could pave way for routine use of stem cells in medicine

LONDON, Jan 29 (Reuters) - In experiments that could open a new era in stem cell biology, scientists have found a cheap and easy way to reprogram mature cells from mice back into an embryonic-like state that allowed them to generate many types of tissue.

The research, described as game-changing by experts in the field, suggests human cells could in future be reprogrammed by the same technique, offering a simpler way to replace damaged cells or grow new organs for sick and injured people.

Chris Mason, chair of regenerative medicine bioprocessing at University College London, who was not involved in the work, said its approach was "the most simple, lowest-cost and quickest method" to generate so-called pluripotent cells - able to develop into many different cell types - from mature cells.

"If it works in man, this could be the game changer that ultimately makes a wide range of cell therapies available using the patient's own cells as starting material - the age of personalized medicine would have finally arrived," he said.

The experiments, reported in two papers in the journal Nature on Wednesday, involved scientists from the RIKEN Center for Developmental Biology in Japan and Brigham and Women's Hospital and Harvard Medical School in the United States.

Beginning with mature, adult cells, researchers let them multiply and then subjected them to stress "almost to the point of death", they explained, by exposing them to various events including trauma, low oxygen levels and acidic environments.

Within days, the scientists found that the cells survived and recovered from the stressful stimulus by naturally reverting into a state similar to that of an embryonic stem cell.

These stem cells created by this exposure to stresses - dubbed STAP cells by the researchers - were then able to differentiate and mature into different types of cells and tissue, depending on the environments they were given.

"If we can work out the mechanisms by which differentiation states are maintained and lost, it could open up a wide range of possibilities for new research and applications using living cells," said Haruko Obokata, who lead the work at RIKEN.

Stem cells are the body's master cells and are able to differentiate into all other types of cells. Scientists say that, by helping to regenerate tissue, they could offer ways of tackling diseases for which there are currently only limited treatments - including heart disease, Parkinson's and stroke.

Read the original:
The future of stem cells is easy & inexpensive: Embryonic regeneration research is ‘game-changing’

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.

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

Contact Information

Available for logged-in reporters only

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.

See original here:
Converting Adult Human Cells to Hair-Follicle-Generating Stem Cells

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.

Irish Examiner Ltd. All rights reserved

Go here to read the rest:
Q&A - Stem cells could offer treatment for a myriad of diseases

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.

Originally posted here:
Are Stem Cells The Cure To Baldness?

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.

Go here to read the rest:
Baldness Cure May Have Inched a Bit Closer

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.

Here is the original post:
Stem cells lab to open in Galway

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."

More here:
Ireland university lab in stem cells move

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

Read the rest here:
New mechanism for genome unpacking in stem cells

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.

See the rest here:
Clinical trial studies vaccine targeting cancer stem cells in brain cancers

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.

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

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.

Link:
Tracing unique cells with mathematics

8 hours ago Endodermal cells, they form organs such as lung, liver and pancreas. Credit: IDR, Helmholtz Zentrum Mnchen

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 renowned 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.

Explore further: Stem cells on the road to specialization

See original here:
Insulin-producing beta cells from stem cells: Scientists decipher early molecular mechanisms of differentiation

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.

Read more here:
Insulin-producing beta cells from stem cells

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.

Read the original:
Statistical Methods Improve Biological Single-Cell Analyses

Renew

Revolutionary skin care with a novel,proprietary approach tocellular aging.

The bodys signals govern skin stem cells, controlling the decision to remain dormant, divide or differentiate (become normal, active tissue cells). Signals flow in path-ways and multiple paths funnel into the common Wnt signaling pathway. Signaling stimulatesskin stem cells to begin the process leading to fibroblasts, keratino-

cytesand other dermal/epidermalcells.

Renewnt skin care products contain the high-end ingredients available today for cosmeceuticals, but also have an entirely new technology,Asymmtate.Unlike many cosmetic agents, Asymmtate has been clinically provento penetrate through the epidermis into the dermis. Makucell currentlyoffers fourtargeted skin careproducts.

Asymmtate AwakensSkin's Stem Cells

Asymmtateis a small molecule that optimizes signaling in the Wnt Pathway and was developed by a team of researchers led byDr. Michael Kahn of the Eli and Edythe Broad Center for Regenerative Medicine at the Keck School of Medicine of the University of Southern California.

Chief Medical Officer

Vice President of Medical &

Scientific Affairs

See the rest here:
Makucell - Best Anti Aging Skin Care

Jan. 19, 2014 Normally, tissue injury triggers a mechanism in cells that tries to repair damaged tissue and restore the skin to a normal, or homeostatic state. Errors in this process can give rise to various problems, such as chronic inflammation, which is a known cause of certain cancers.

"It has been noted that cancer resembles a state of chronic wound healing, in which the wound-healing program is erroneously activated and perpetuated," says Professor Adrian Krainer of Cold Spring Harbor Laboratory (CSHL). In a paper published today in Nature Structural & Molecular Biology, a team led by Dr. Krainer reports that a protein they show is normally involved in healing wounds and maintaining homeostasis in skin tissue is also, under certain conditions, a promoter of invasive and metastatic skin cancers.

The protein, called SRSF6, is what biologists call a splicing factor: it is one of many proteins involved in an essential cellular process called splicing. In splicing, an RNA "message" copied from a gene is edited so that it includes only the portions needed to instruct the cell how to produce a specific protein. The messages of most genes can be edited in multiple ways, using different splicing factors; thus, a single gene can give rise to multiple proteins, with distinct functions.

The SRSF6 protein, while normally contributing to wound healing in skin tissue, when overproduced can promote abnormal growth of skin cells and cancer, Krainer's team demonstrated in experiments in mice. Indeed, they determined the spot on a particular RNA message -- one that encodes the protein tenascin C -- where SRSF6 binds abnormally, giving rise to alternate versions of the tenascin C protein that are seen in invasive and metastatic cancers.

The CSHL team also found that overproduction of SRSF6 in mice results in the depletion of a type of stem cell called Lgr6+. These skin stem cells reside in the upper part of the hair follicle and participate in wound healing when tissue is damaged. Thus, aberrant alternative splicing by SRSF6 on the one hand increases cell proliferation, but on the other hand prevents the process by which proliferating cells mature. "The cells remain in an abnormal activation state that would otherwise be temporary during normal tissue repair. More studies are needed to understand this phenomenon in detail," says Mads Jensen, Ph.D., first author of the new paper who performed the experiments as a postdoctoral researcher in the Krainer lab.

Continue reading here:
Overexpression of splicing protein in skin repair causes early changes seen in skin cancer