Archive for the ‘Skin Stem Cells’ Category

PHILADELPHIA, Jan. 29 (UPI) -- U.S. researchers say they used epithelial stem cells to regenerate different cell types of human skin and hair follicles that may help those going bald.

Dr. Xiaowei "George" Xu, associate professor of pathology and laboratory medicine and dermatology at the Perelman School of Medicine at University of Pennsylvania, and colleagues at the New Jersey Institute of Technology, said they started with human skin cells called dermal fibroblasts.

By adding three genes, they converted those cells into induced pluripotent stem cells, which have the capability to differentiate into any cell types in the body. They then converted the induced pluripotent stem 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 induced pluripotent stem cells into keratinocytes, Xu's team demonstrated that by carefully controlling the timing of the growth factors the cells received, they could force the induced pluripotent stem cells to generate large numbers of epithelial stem cells.

The team succeeded in turning more than 25 percent of the induced pluripotent stem cells into epithelial stem cells in 18 days.

Those cells were then purified using the proteins they expressed on their surfaces.

"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 said in a statement. "And those cells have many potential applications including wound healing, cosmetics and hair regeneration."

The findings were published in Nature Communications.

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Hair-follicle generating stem cells may help with baldness

WASHINGTON: In a breakthrough, scientists claim to have successfully transformed human skin cells into hair-follicle-generating stem cells for the first time.

Xiaowei "George" Xu from the Perelman School of Medicine, University of Pennsylvania, and colleagues have found 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 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.

The 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.

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Human skin cells help regrow hair in mice

BOSTON, Jan. 29 (UPI) -- Scientists have stumbled upon a simple way to create stem cells without embryos -- by bathing healthy adult cells in an acid bath for 30 minutes.

A team of researchers from Boston and Japan were able to transform mature blood cells from mice into the equivalent of stem cells by introducing them to an acidic environment. This is the first time that stem cells have been created without having to introduce outside DNA into the cells.

"The fate of adult cells can be drastically converted by exposing mature cells to an external stress or injury. This finding has the potential to reduce the need to utilize both embryonic stem cells and DNA-manipulated iPS cells," said senior author Charles Vacanti.

The latest development, published in the journal Nature, could be used to create stems cells easily and quickly. Stem cells are known to become other kinds of cells, and have the potential to regenerate injured parts of the body. Embryos are a controversial source of such cells, though more are under study, including Nobel-winning research in 2006 that showed skin cells could be genetically reprogrammed to become stem cells.

The researchers aren't sure how this happens, but have hypothesized that it could be due to hidden cell functions that are triggered by external stimuli.

Researchers are now attempting to use the same method to convert human blood cells and believe that if successful it could be used in not only regenerative treatment but cancer treatment as well.

"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 first author Haruko Obokata, of the RIKEN Center for Developmental Biology.

[Brigham and Women's Hospital] [RIKEN Center for Developmental Biology] [Nature]

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Scientists find faster, easier way to create stem 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...

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Carving out a Niche for Stem Cells - Video

This is big.

Scientists have found a way to create embryonic stem cells without using an embryo or without introducing genetic material. The discovery could revolutionize medicine by giving doctors a way to repair diseased and damaged tissue think heart disease, blindness, skin burns with organs and tissue grown from the patients own cells.

Cloning Creates Human Embryonic Stem Cells

The researchers, led by Haruko Obokata from the Riken Center for Developmental Biology in Kobe, Japan, found that by when they applied various stresses to white blood cells, such as bathing them in acid or putting them in a low-oxygen environment, nearly bringing them to the brink of death, some of the cells lost their blood identity and reverted to a state equivalent to an embryonic stem cell.

They call these cells STAP, for stimulus-triggered acquisition of pluripotency.

When the scientists transferred the STAP cells to a special growth-promoting solution, they began to multiply and look like embryonic stem cells, which can grow into any type of cell skin, bone, organ depending on the environment into which they were placed.

And when the cells were injected into mice embryos, they contributed to the overall tissue of the baby mice, something that researchers didnt think would be possible.

Not only is the approach faster and far cheaper than current methods, but it eliminates the controversy surrounding embryonic stem cell research, which requires the destruction of an embryo, raising ethical concerns. The new approach also avoids the genetic risks associated with the alternative to the embryonic method, called induced pluripotent stem (iPS) cells. That technique requires the introduction of genetic material into a cell, and has lead to tumor growth in some cases.

Stem Cell Treatment Cures Blindness

Inspiration for the research came from techniques already used in labs and in gardening, where a change in the physical environment can alter a cells identity. In the lab, for example, frog skin cells can be switched to brain cells if exposed to a solution with a low pH. And botanists can grow a new plant by creating a plant callus, a node of plant cells created from a physical injury to an existing plant.

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Groundbreaking: Embryonic Stem Cells Made With Acid

Malcolm Ritter, The Associated Press Published Wednesday, January 29, 2014 10:57AM EST

NEW YORK -- A simple lab treatment can turn ordinary cells from mice into stem cells, according to a surprising study that hints at a possible new way to grow tissue for treating illnesses like diabetes and Parkinson's disease.

Researchers in Boston and Japan exposed cells from spleens of newborn mice to a more acidic environment that they're used to. In lab tests, that turned them into stem cells, showing enough versatility to produce the tissues of a mouse embryo, for example.

Cells from skin, muscle, fat and other tissue of newborn mice appeared to go through the same change, which could be triggered by exposing cells to any of a variety of stressful situations, researchers said.

Scientists hope to harness stem cells to replace defective tissue in a wide variety of diseases. By making stem cells from the patient, they can get around the problem of transplant rejection.

Human cells are now routinely turned into so-called "iPS" stem cells. That involves reprogramming an ordinary cell by slipping genes or substances into its nucleus. The new method, in contrast, lets the cell change its own behaviour after researchers have applied an external stress.

"It's very simple to do. I think you could do this actually in a college lab," said Dr. Charles Vacanti of Brigham and Women's Hospital in Boston, an author of two papers published online Wednesday by the journal Nature.

Vacanti also acknowledged that if the technique works with human cells, it could conceivably provide a new potential route for cloning people. He has no interest in doing that, he said, but "it is a concern."

Another author, Haruko Obokata of the RIKEN Center for Developmental Biology in Kobe, Japan, said researchers are now studying whether the technique works with human cells. She also said it's premature to compare it to iPS technology in terms of potential medical uses.

Experts not connected to the study said the results are surprising, and that it's too soon to know their practical implications.

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Simple technique produces stem cells in mice

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

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

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.

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Bye bye baldness? Researchers regrow hair using skin cells

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

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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Are Stem Cells The Cure To Baldness?

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

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

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

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.'

Stem cells are best described as serving as the body's repair mechanism and in recent years science has isolated them from tissues such as bone marrow and fat to recreate them in laboratory settings.

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Ireland uni lab in stem cells move

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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Ireland university lab in stem cells move

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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Clinical trial studies vaccine targeting cancer stem cells in brain cancers

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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

VN:F [1.9.22_1171]

Several recent reports on ongoing clinical trials for gene therapies indicate that even preliminary studies with only a handful of patients can yield results with the potential to alter the course of the entire field. So after each description below, I offer a DNA Science lesson learned assessment: why the study is important.

INTO THE BRAIN PARKINSONS DISEASE

Gene therapy typically delivers a functioning version of a gene to cells needing it. Investigators Stphane Palfi MD of AP-HP, Groupe Henri-Mondor Albert-Chenevier in Crteil, France and Roger Barker, PhD, at Addenbrookes Hospital in Cambridge, UK, have expanded the reach of gene therapy by delivering the trio of genes whose encoded proteins enable cells to make dopamine, the neurotransmitter thats depleted as Parkinsons disease (PD) progresses. Preliminary results on the gene therapy appear inThe Lancet.Oxford Biomedica, a company developing gene-based medicines, is funding the trial of the triplo-gene therapy for Parkinsons, called ProSavin.

Gene therapy enables cells of the striatum to use the 3 genes that make dopamine.

In a healthy brain, neurons in the substantia nigra make dopamine. Their axons project to the striatum, where they release the neurotransmitter so neurons there can sop it up. Three enzymes control dopamine synthesis: two convert the amino acid tyrosine to levodopa, and a third converts the levodopa to dopamine.

Treating PD is an ever-changing question of balance. Oral levodopa can offset the dopamine deficit, but after a few years, motor symptoms develop. These include uncontrollable movements (tardive dyskinesia) and on-off phenomena, which are periods of improved mobility interspersed with periods of impairment, sometimes severe.

Where there are missing enzymes, gene therapy is an option, and several have been tried for Parkinsons disease. The safest gene therapy vector (a disabled virus that delivers the gene), adeno-associate virus (AAV), cant carry a very large payload, only one smallish gene at a time. So the researchers turned to a larger vehicle to deliver the trio of genes, the lentivirus that causes swamp fever in horses, equine infectious anemia (EIA) virus. Many gene therapy experiments use a more familiar lentivirus HIV.

A horse virus delivers Parkinsons gene therapy.

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Gene Therapy News: Brain, Skin, Eye - DNA Science Blog

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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Tracing unique cells with mathematics

12 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

Read the rest 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.

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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 more from the original source:
Statistical Methods Improve Biological Single-Cell Analyses

7 hours ago The images show the microtubule-based spindle fibers (red), chromosomes (blue), and their kinetochores (green). Microtubules align chromosomes in the middle of the spindle in the presence of the newly discovered protein called BuGZ (+BuGZ), but mis-aligned in its absence (-BuGZ). Chromosome misalignment leads to its mis-segregation during cell division. Scale bar, 5 microns. Credit: Yixian Zheng. Credit: Yixian Zheng

As all school-children learn, cells divide using a process called mitosis, which consists of a number of phases during which duplicate copies of the cell's DNA-containing chromosomes are pulled apart and separated into two distinct cells. Losing or gaining chromosomes during this process can lead to cancer and other diseases, so understanding mitosis is important for developing therapeutic strategies.

New research from a team led by Carnegie's Yixian Zheng focused on one important part of this process. Her results improve our understanding of how cell division gives rise to two daughter cells with an equal complement of chromosomes. It is published by Developmental Cell.

Cell division is helped along by a complex of more than 90 proteins, called a kinetochore, interacting with scaffolding-like structural fibers called microtubules. Together the kinetochore and microtubules provide the structure and force that pull the two duplicate halves of the chromosome apart and direct them to each daughter cell.

By looking beyond the microtubules and kinetochores themselves, Zheng's team identified a protein that regulates the interactions between the kinetochore and the microtubule fibers. Using super resolution microscopy, they were able to hone in on one particular phase of this process, namely the way that microtubules are "captured" by the kinetochore to promote proper alignment of the chromosomes in a way that facilitates equal partition of duplicated DNA.

"The study of mitosis has focused on microtubules and kinetochores, the most prominent structure that researchers observe. Our work demonstrates the importance of expanding the scope of study to include other cellular components because this is critical to achieving an in depth understanding of the mechanisms underlying chromosome alignment in preparation for dividing the DNA into two new cells." Zheng said.

Explore further: Discovery of cell division 'master controller' may improve understanding and treatment of cancer

In a study to be published in the journal Nature, two Dartmouth researchers have found that the protein cyclin A plays an important but previously unknown role in the cell division process, acting as a master controller to ens ...

Ludwig researchers Arshad Desai and Christopher Campbell, a post-doctoral fellow in his laboratory, were conducting an experiment to parse the molecular details of cell division about three years ago, when they engineered ...

(Phys.org) Researchers at Warwick Medical School have identified the key role played by a team of proteins in the process of mitosis. Working out how to control them may give scientists a way to destroy ...

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What makes cell division accurate?

7 hours ago This is a model for maintenance of proper microtubule polarity in dendrites. Polymerizing microtubules entering junctions encounter existing static filaments. A complex consisting of end-binding protein 1 (EB1) and a kinesin molecular motor binds to the tip of the growing filament and moves along the static filament to co-align the filaments and maintain proper uniform orientation. The present work demonstrates that an EB1-kinesin complex is able to steer a growing microtubule in this manner without the requirement for any other cellular components. Credit: William Hancock, Penn State

Tiny protein motors in cells can steer microtubules in the right direction through branching nerve cell structures, according to Penn State researchers who used laboratory experiments to test a model of how these cellular information highways stay organized in living cells.

"We proposed a model of how it works in vivo, in the living cell," said Melissa Rolls, associate professor of biochemistry and molecular biology. "But because of the complexity of the living cells, we couldn't tell if the model was possible."

Rolls then collaborated with William O. Hancock, professor of biomedical engineering, who was already working on the tiny kinesin motors that move materials throughout the cell, to test the model in the laboratory, in vitro.

"Kinesins are little machines that use chemical energy to generate mechanical forces sufficient to carry materials through the cell," said Hancock.

Cells produce enzymes, proteins and signaling chemicals in the center of the cell, and these materials are then moved to other cell areas by kinesin motors. Dendrites in nerves cells are very long, and motors need to transport molecules relatively long distances on microtubules that are constantly forming and dissolving within the cell. Because dendrites branch, the researchers wondered how the microtubules themselves move in the right direction.

Working with Yalei Chen, graduate student in cell and developmental biology in the Huck Institutes of the Life Sciences, the researchers found that kinesin motors can not only transport molecules along the tubules, but can redirect the ends of the tubules to enter the proper branch of the dendrite. They report their findings online today (Jan. 23) in Current Biology.

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In the laboratory, the researchers grew microtubules under the microscope and used protein engineering to attach a kinesin motor to EB1a protein that binds to the growing end of microtubules.

"One of the reasons we thought the model might not work is that the molecule EB1 grabs the plus end of the microtubule very loosely," said Rolls. "We were unsure how something so dynamic could hold the forces, but it does."

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Experiments show hypothesis of microtubule steering accurate