Category Archives: Stem Cells

When researchers and, especially, the general public became aware of the potential medical uses of stem cells the possibilities seemed endless. The National Institutes of Health said this: ... a renewable source of replacement cells and tissues to treat a myriad of diseases, conditions, and disabilities, including Parkinsons disease, amyotrophic lateral sclerosis, spinal cord injury, burns, heart disease, diabetes, and arthritis.

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EDITORIAL: London researchers illustrate potential of stem cell therapies

The activity of four transcription factors -- proteins that regulate the expression of other genes -- appears to distinguish the small proportion of glioblastoma cells responsible for the aggressiveness and treatment resistance of the deadly brain tumor. The findings by a team of Massachusetts General Hospital (MGH) investigators, which will be published in the April 24 issue of Cell and are receiving advance online release, support the importance of epigenetics -- processes controlling whether or not genes are expressed -- in cancer pathology and identify molecular circuits that may be targeted by new therapeutic approaches.

"We have identified a code of 'molecular switches' that control a very aggressive subpopulation of brain cancer cells, so-called glioblastoma stem cells," says Mario Suv, MD, PhD, of the MGH Department of Pathology and Center for Cancer Research, co-lead author of the Cell article. "Understanding what drives these aggressive cells will give us insights into alternative ways of eliminating them and potentially changing the course of this very deadly tumor."

Normal biological development follows an orderly hierarchical progression from stem cells, capable of differentiating into almost any type of cell, to progenitor cells, giving rise to specific subtypes of cells and tissues, to fully differentiated cells. While the process usually proceeds in a one-way direction, artificially inducing the activity of key transcription factors can reprogram differentiated cells back into a stem-like state, a discovery honored with the 2012 Nobel prize.

Small populations of adult stem cells with somewhat limited developmental potential are responsible for the body's ability to heal injuries and replace worn out cells and tissues, and evidence is growing that rare cancer stem cells are responsible for the uncontrolled growth of some malignant tumors, including glioblastoma. Several studies have used cell-surface markers -- proteins found on the outer membranes of tumor cells -- to identify glioblastoma stem cells; but the specific markers used have been controversial and cannot reflect molecular processes going on within tumor cells. The current study was designed to clarify the cellular hierarchy underlying glioblastoma, to identify epigenetic factors that distinguish glioblastoma stem cells from more differentiated tumor cells and to suggest potential therapies targeting those factors.

In a series of experiments, the researchers first identified a set of 19 transcription factors that were expressed at significantly greater levels in cultured human glioblastoma stem cells capable of tumor propagation than in differentiated tumor cells. Testing each of these factors for their ability to return differentiated tumor cells to a stem-like state, identified a combination of four -- POU3F2, SOX2, SALL2 and OLIG2 -- that was able to reprogram differentiated tumor cells back into glioblastoma stem cells, both in vitro and in an animal model.

The investigators then confirmed that these four factors and their corresponding regulatory elements -- the DNA segments to which transcription factors bind -- were active in from 2 to 7 percent of human glioblastoma cells, cells that also expressed a known stem cell marker. They also showed that inhibiting the action of an important regulatory protein complex that involves a known target gene of one of the core transcription factors -- a gene active in stem-like glioblastoma cells but not differentiated cells -- caused glioblastoma stem cells to lose their stem-like properties and die.

"This study brings us back to the fundamental idea that there are many reasons that cancer cells can be aggressive," explains senior author Bradley Bernstein, MD, PhD, of MGH Pathology and the MGH Cancer Center. "Just as normal cells with the same genome differentiate into many different cell types, a single tumor characterized by specific genetic mutations can contain many different types of cells -- stem-like and more differentiated cells -- with the difference being rooted in their epigenetic information. Identifying the drivers of these different cellular states in glioblastoma stem cells could offer us the best opportunity for treating what remains an extremely difficult-to -treat tumor."

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The above story is based on materials provided by Massachusetts General Hospital. Note: Materials may be edited for content and length.

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Transcription factors distinguishing glioblastoma stem cells identified

PUBLIC RELEASE DATE:

10-Apr-2014

Contact: Sue McGreevey smcgreevey@partners.org 617-724-2764 Massachusetts General Hospital

The activity of four transcription factors proteins that regulate the expression of other genes appears to distinguish the small proportion of glioblastoma cells responsible for the aggressiveness and treatment resistance of the deadly brain tumor. The findings by a team of Massachusetts General Hospital (MGH) investigators, which will be published in the April 24 issue of Cell and are receiving advance online release, support the importance of epigenetics processes controlling whether or not genes are expressed in cancer pathology and identify molecular circuits that may be targeted by new therapeutic approaches.

"We have identified a code of 'molecular switches' that control a very aggressive subpopulation of brain cancer cells, so-called glioblastoma stem cells," says Mario Suv, MD, PhD, of the MGH Department of Pathology and Center for Cancer Research, co-lead author of the Cell article. "Understanding what drives these aggressive cells will give us insights into alternative ways of eliminating them and potentially changing the course of this very deadly tumor."

Normal biological development follows an orderly hierarchical progression from stem cells, capable of differentiating into almost any type of cell, to progenitor cells, giving rise to specific subtypes of cells and tissues, to fully differentiated cells. While the process usually proceeds in a one-way direction, artificially inducing the activity of key transcription factors can reprogram differentiated cells back into a stem-like state, a discovery honored with the 2012 Nobel prize.

Small populations of adult stem cells with somewhat limited developmental potential are responsible for the body's ability to heal injuries and replace worn out cells and tissues, and evidence is growing that rare cancer stem cells are responsible for the uncontrolled growth of some malignant tumors, including glioblastoma. Several studies have used cell-surface markers proteins found on the outer membranes of tumor cells to identify glioblastoma stem cells; but the specific markers used have been controversial and cannot reflect molecular processes going on within tumor cells. The current study was designed to clarify the cellular hierarchy underlying glioblastoma, to identify epigenetic factors that distinguish glioblastoma stem cells from more differentiated tumor cells and to suggest potential therapies targeting those factors.

In a series of experiments, the researchers first identified a set of 19 transcription factors that were expressed at significantly greater levels in cultured human glioblastoma stem cells capable of tumor propagation than in differentiated tumor cells. Testing each of these factors for their ability to return differentiated tumor cells to a stem-like state, identified a combination of four POU3F2, SOX2, SALL2 and OLIG2 that was able to reprogram differentiated tumor cells back into glioblastoma stem cells, both in vitro and in an animal model.

The investigators then confirmed that these four factors and their corresponding regulatory elements the DNA segments to which transcription factors bind were active in from 2 to 7 percent of human glioblastoma cells, cells that also expressed a known stem cell marker. They also showed that inhibiting the action of an important regulatory protein complex that involves a known target gene of one of the core transcription factors a gene active in stem-like glioblastoma cells but not differentiated cells caused glioblastoma stem cells to lose their stem-like properties and die.

"This study brings us back to the fundamental idea that there are many reasons that cancer cells can be aggressive," explains senior author Bradley Bernstein, MD, PhD, of MGH Pathology and the MGH Cancer Center. "Just as normal cells with the same genome differentiate into many different cell types, a single tumor characterized by specific genetic mutations can contain many different types of cells stem-like and more differentiated cells with the difference being rooted in their epigenetic information. Identifying the drivers of these different cellular states in glioblastoma stem cells could offer us the best opportunity for treating what remains an extremely difficult-to -treat tumor."

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Researchers identify transcription factors distinguishing glioblastoma stem cells

Professor Alexander Seifalian poses for photographs with a synthetic polymer nose at his research facility in the Royal Free Hospital in London, Monday, March 31, 2014. In a north London hospital, scientists are growing noses, ears and blood vessels in the laboratory in a bold attempt to make body parts using stem cells. AP

In a north London hospital, scientists are growing noses, ears and blood vessels in the laboratory in a bold attempt to make body parts using stem cells.

It is among several labs around the world, including in the U.S., that are working on the futuristic idea of growing custom-made organs in the lab.

5 Photos

In a north London hospital, scientists are growing noses, ears and blood vessels in attempt to make body parts using stem cells

"It's like making a cake," said Alexander Seifalian at University College London, the scientist leading the effort. "We just use a different kind of oven."

During a recent visit to his lab, Seifalian showed off a sophisticated machine used to make molds from a polymer material for various organs.

Last year, he and his team made a nose for a British man who lost his to cancer. Scientists added a salt and sugar solution to the mold of the nose to mimic the somewhat sponge-like texture of the real thing. Stem cells were taken from the patient's fat and grown in the lab for two weeks before being used to cover the nose scaffold. Later, the nose was implanted into the man's forearm so that skin would grow to cover it.

Seifalian said he and his team are waiting for approval from regulatory authorities to transfer the nose onto the patient's face but couldn't say when that might happen

The potential applications of lab-made organs appear so promising even the city of London is getting involved: Seifalian's work is being showcased on Tuesday as Mayor Boris Johnson announces a new initiative to attract investment to Britain's health and science sectors so spin-off companies can spur commercial development of the pioneering research.

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Ears, noses grown from stem cells in lab dishes

LONDON In a north London hospital, scientists are growing noses, ears and blood vessels in the laboratory in a bold attempt to make body parts using stem cells.

It is among several labs around the world, including in the US, that are working on the futuristic idea of growing custom-made organs in the lab.

While only a handful of patients have received the British lab-made organs so far including tear ducts, blood vessels and windpipes researchers hope they will soon be able to transplant more types of body parts into patients, including what would be the worlds first nose made partly from stem cells.

Its like making a cake, said Alexander Seifalian at University College London, the scientist leading the effort. We just use a different kind of oven.

Dr. Michelle Griffin, a plastic surgery research fellow, holds a synthetic polymer ear.Photo: AP

During a recent visit to his lab, Seifalian showed off a sophisticated machine used to make molds from a polymer material for various organs.

Last year, he and his team made a nose for a British man who lost his to cancer. Scientists added a salt and sugar solution to the mold of the nose to mimic the somewhat sponge-like texture of the real thing. Stem cells were taken from the patients fat and grown in the lab for two weeks before being used to cover the nose scaffold. Later, the nose was implanted into the mans forearm so that skin would grow to cover it.

Seifalian said he and his team are waiting for approval from regulatory authorities to transfer the nose onto the patients face but couldnt say when that might happen.

The potential applications of lab-made organs appear so promising, even the city of London is getting involved: Seifalians work is being showcased on Tuesday as Mayor Boris Johnson announces a new initiative to attract investment to Britains health and science sectors so spin-off companies can spur commercial development of the pioneering research.

The polymer material Seifalian uses for his organ scaffolds has been patented and hes also applied for patents for their blood vessels, tear ducts and windpipe. He and his team are creating other organs including coronary arteries and ears. Later this year, a trial is scheduled to start in India and London to test lab-made ears for people born without them.

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Sci-fi meets reality as stem cells are turned into noses, ears

London's Royal Free hospital is among several in the world that are working on the futuristic idea of growing custom-made organs in the lab Few have received the lab-made organs so far - including ears and windpipes - but researchers hope they will soon transplant more They hope to transplant world's first nose made partly from stem cells

By Associated Press and Ellie Zolfagharifard

Published: 05:38 EST, 8 April 2014 | Updated: 12:09 EST, 8 April 2014

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At London's Royal Free hospital, scientists are growing noses, ears and blood vessels in the laboratory in a bold attempt to make body parts using stem cells.

It is among several labs around the world, including in the U.S., that are working on the futuristic idea of growing custom-made organs in the lab.

Only a handful of patients have received the British lab-made organs so far - including tear ducts, blood vessels and windpipes.

But researchers hope they will soon be able to transplant more types of body parts into patients, including what would be the world's first nose made partly from stem cells.

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British scientists make custom-made body parts using stem cells

Treating ACL Tears with Stem Cells - Dr. Ben Newton Regenexx-ACL
Regenexx-ACL is a targeted stem cell procedure for treating ACL tear injuries using stem cells from your own body. Dr. Ben Newton discusses this unique procedure designed to help individuals...

By: Regenexx

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Treating ACL Tears with Stem Cells - Dr. Ben Newton & Regenexx-ACL - Video

PUBLIC RELEASE DATE:

4-Apr-2014

Contact: Harry Dayantis h.dayantis@ucl.ac.uk 44-020-310-83844 University College London

A new way to artificially control muscles using light, with the potential to restore function to muscles paralysed by conditions such as motor neuron disease and spinal cord injury, has been developed by scientists at UCL and King's College London.

The technique involves transplanting specially-designed motor neurons created from stem cells into injured nerve branches. These motor neurons are designed to react to pulses of blue light, allowing scientists to fine-tune muscle control by adjusting the intensity, duration and frequency of the light pulses.

In the study, published this week in Science, the team demonstrated the method in mice in which the nerves that supply muscles in the hind legs were injured. They showed that the transplanted stem cell-derived motor neurons grew along the injured nerves to connect successfully with the paralyzed muscles, which could then be controlled by pulses of blue light.

"Following the new procedure, we saw previously paralysed leg muscles start to function," says Professor Linda Greensmith of the MRC Centre for Neuromuscular Diseases at UCL's Institute of Neurology, who co-led the study. "This strategy has significant advantages over existing techniques that use electricity to stimulate nerves, which can be painful and often results in rapid muscle fatigue. Moreover, if the existing motor neurons are lost due to injury or disease, electrical stimulation of nerves is rendered useless as these too are lost."

Muscles are normally controlled by motor neurons, specialized nerve cells within the brain and spinal cord. These neurons relay signals from the brain to muscles to bring about motor functions such as walking, standing and even breathing. However, motor neurons can become damaged in motor neuron disease or following spinal cord injuries, causing permanent loss of muscle function resulting in paralysis

"This new technique represents a means to restore the function of specific muscles following paralysing neurological injuries or disease," explains Professor Greensmith. "Within the next five years or so, we hope to undertake the steps that are necessary to take this ground-breaking approach into human trials, potentially to develop treatments for patients with motor neuron disease, many of whom eventually lose the ability to breathe, as their diaphragm muscles gradually become paralysed. We eventually hope to use our method to create a sort of optical pacemaker for the diaphragm to keep these patients breathing."

The light-responsive motor neurons that made the technique possible were created from stem cells by Dr Ivo Lieberam of the MRC Centre for Developmental Neurobiology, King's College London.

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Light-activated neurons from stem cells restore function to paralyzed muscles

Charlottesville, VA (PRWEB) April 04, 2014

Scientists at the University of Virginia School of Medicine have overcome one of the greatest challenges in biology and taken a major step toward being able to grow whole organs and tissues from stem cells. By manipulating the appropriate signaling, the UVA researchers have turned embryonic stem cells into a fish embryo, essentially controlling embryonic development.

The research will have dramatic impact on the future use of stem cells to better the human condition, providing a framework for future studies in the field of regenerative medicine aimed at constructing tissues and organs from populations of cultured pluripotent cells.

In accomplishing this, UVA scientists Bernard and Chris Thisse have overcome the most massive of biological barriers. We have generated an animal by just instructing embryonic cells the right way, said Chris Thisse, PhD, of the School of Medicines Department of Cell Biology.

The importance of that is profound. If we know how to instruct embryonic cells, she said, we can pretty much do what we want. For example, scientists will be able one day to instruct stem cells to grow into organs needed for transplant.

Directing Embryonic Development The researchers were able to identify the signals sufficient for starting the cascade of molecular and cellular processes that lead to a fully developed fish embryo. With this study came an answer to the longstanding question of how few signals can initiate the processes of development: amazingly, only two.

The study has shed light on the important roles these two signals play for the formation of organs and full development of a zebrafish embryo. Moreover, the Thisses are now able to direct embryonic development and formation of tissues and organs by controlling signal locations and concentrations.

The embryo they generated was smaller than a normal embryo, because they instructed a small pool of embryonic stem cells, but otherwise he has everything in terms of appropriate development, said Bernard Thisse, PhD, of the Department of Cell Biology.

Their next steps will be to attempt to reproduce their findings using mice. They expect molecular and cellular mechanisms will be extremely similar in mice and other mammals including humans.

Published in Science The findings have been published online by Science and will appear in a forthcoming print edition of the prestigious journal. The article was authored by UVAs Peng-Fei Xu, Nathalie Houssin, Karine F. Ferri-Lagneau, Bernard Thisse and Christine Thisse.

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UVA Smashes Barrier to Growing Organs from Stem Cells

April 4, 2014

The University of Virginia School of Medicine has made a major scientific breakthrough. Scientists working in the Department of Cell Biology have been able to create a fish embryo using stem cells.

The breakthrough comes after years of research into how embryonic stem cells work. Scientists were able to determine that it only takes two signals to start the process of development that lead to the fish embryo.

This discovery is also a major step toward being able to grow entire organs using stem cells.

"Of course now, of we know how to instruct the cells and make heart cells," says Dr. Chris Thisse. "The hope - not for tomorrow, of course- but the hope is just, you can, you know, make a new heart."

The new embryo, while slightly smaller than a normal fish embryo, has everything that an average fish would have at this stage in development.

Scientists say the next step is to test the stem cells of mice to see if they can trigger the development of a mouse embryo.

If the results can be reproduced, scientists are certain they could complete successful tests on human stem cells as well.

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Researchers at UVa. Create Fish Embryo from Stem Cells