Category Archives: Stem Cells

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When infections occur in the body, stem cells in the blood often jump into action by multiplying and differentiating into mature immune cells that can fight off illness. But repeated infections and inflammation can deplete these cell populations, potentially leading to the development of serious blood conditions such as cancer. Now, a team of researchers led by biologists at the California Institute of Technology (Caltech) has found that, in mouse models, the molecule microRNA-146a (miR-146a) acts as a critical regulator and protector of blood-forming stem cells (called hematopoietic stem cells, or HSCs) during chronic inflammation, suggesting that a deficiency of miR-146a may be one important cause of blood cancers and bone marrow failure.

The team came to this conclusion by developing a mouse model that lacks miR-146a. RNA is a polymer structured like DNA, the chemical that makes up our genes. MicroRNAs, as the name implies, are a class of very short RNAs that can interfere with or regulate the activities of particular genes. When subjected to a state of chronic inflammation, mice lacking miR-146a showed a decline in the overall number and quality of their HSCs; normal mice producing the molecule, in contrast, were better able to maintain their levels of HSCs despite long-term inflammation. The researchers' findings are outlined in the May 21 issue of the new journal eLIFE.

"This mouse with genetic deletion of miR-146a is a wonderful model with which to understand chronic-inflammation-driven tumor formation and hematopoietic stem cell biology during chronic inflammation," says Jimmy Zhao, the lead author of the study and a MD/PhD student in the Caltech laboratory of David Baltimore, the Robert Andrews Millikan Professor of Biology. "It was surprising that a single microRNA plays such a crucial role. Deleting it produced a profound and dramatic pathology, which clearly highlights the critical and indispensable function of miR-146a in guarding the quality and longevity of HSCs."

The study findings provide, for the first time, a detailed molecular connection between chronic inflammation, and bone marrow failure and diseases of the blood. These findings could lead to the discovery and development of anti-inflammatory molecules that could be used as therapeutics for blood diseases. In fact, the researchers believe that miR-146a itself may ultimately become a very effective anti-inflammatory molecule, once RNA molecules or mimetics can be delivered more efficiently to the cells of interest.

The new mouse model, Zhao says, also mimics important aspects of human myelodysplastic syndrome (MDS)a form of pre-leukemia that often causes severe anemia, can require frequent blood transfusions, and usually leads to acute myeloid leukemia. Further study of the model could lead to a better understanding of the condition and therefore potential new treatments for MDS.

"This study speaks to the importance of keeping chronic inflammation in check and provides a good rationale for broad use of safer and more effective anti-inflammatory molecules," says Baltimore, who is a coauthor of the study. "If we can understand what cell types and proteins are critically important in chronic-inflammation-driven tumor formation and stem cell exhaustion, we can potentially design better and safer drugs to intervene."

Explore further: A potential biomarker for pregnancy-associated heart disease?

More information: "MicroRNA-146a acts as a guardian of the quality and longevity of hematopoietic stem cells in mice," eLIFE, 2013.

Peripartum cardiomyopathy (PPCM) is a deterioration in cardiac function that occurs in pregnant women during the last month or in the months following their pregnancy. This disorder can occur in women with no prior history ...

Originally posted here:
Keeping stem cells strong: Biologists show that an RNA molecule protects stem cells during inflammation

May 21, 2013 When infections occur in the body, stem cells in the blood often jump into action by multiplying and differentiating into mature immune cells that can fight off illness. But repeated infections and inflammation can deplete these cell populations, potentially leading to the development of serious blood conditions such as cancer. Now, a team of researchers led by biologists at the California Institute of Technology (Caltech) has found that, in mouse models, the molecule microRNA-146a (miR-146a) acts as a critical regulator and protector of blood-forming stem cells (called hematopoietic stem cells, or HSCs) during chronic inflammation, suggesting that a deficiency of miR-146a may be one important cause of blood cancers and bone marrow failure.

The team came to this conclusion by developing a mouse model that lacks miR-146a. RNA is a polymer structured like DNA, the chemical that makes up our genes. MicroRNAs, as the name implies, are a class of very short RNAs that can interfere with or regulate the activities of particular genes. When subjected to a state of chronic inflammation, mice lacking miR-146a showed a decline in the overall number and quality of their HSCs; normal mice producing the molecule, in contrast, were better able to maintain their levels of HSCs despite long-term inflammation. The researchers' findings are outlined in the May 21 issue of the new journal eLIFE.

"This mouse with genetic deletion of miR-146a is a wonderful model with which to understand chronic-inflammation-driven tumor formation and hematopoietic stem cell biology during chronic inflammation," says Jimmy Zhao, the lead author of the study and a MD/PhD student in the Caltech laboratory of David Baltimore, the Robert Andrews Millikan Professor of Biology. "It was surprising that a single microRNA plays such a crucial role. Deleting it produced a profound and dramatic pathology, which clearly highlights the critical and indispensable function of miR-146a in guarding the quality and longevity of HSCs."

The study findings provide, for the first time, a detailed molecular connection between chronic inflammation, and bone marrow failure and diseases of the blood. These findings could lead to the discovery and development of anti-inflammatory molecules that could be used as therapeutics for blood diseases. In fact, the researchers believe that miR-146a itself may ultimately become a very effective anti-inflammatory molecule, once RNA molecules or mimetics can be delivered more efficiently to the cells of interest.

The new mouse model, Zhao says, also mimics important aspects of human myelodysplastic syndrome (MDS) -- a form of pre-leukemia that often causes severe anemia, can require frequent blood transfusions, and usually leads to acute myeloid leukemia. Further study of the model could lead to a better understanding of the condition and therefore potential new treatments for MDS.

"This study speaks to the importance of keeping chronic inflammation in check and provides a good rationale for broad use of safer and more effective anti-inflammatory molecules," says Baltimore, who is a coauthor of the study. "If we can understand what cell types and proteins are critically important in chronic-inflammation-driven tumor formation and stem cell exhaustion, we can potentially design better and safer drugs to intervene."

Funding for the research outlined in the eLIFE paper, titled "MicroRNA-146a acts as a guardian of the quality and longevity of hematopoietic stem cells in mice," was provided by the National Institute of Allergy and Infectious Disease; the National Heart, Lung, and Blood Institute; and the National Cancer Institute. Yvette Garcia-Flores, the lead technician in Baltimore's lab, also contributed to the study along with Dinesh Rao from UCLA and Ryan O'Connell from the University of Utah. eLIFE, a new open-access, high-impact journal, is backed by three of the world's leading funding agencies, the Howard Hughes Medical Institute, the Max Planck Society, and the Wellcome Trust.

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Keeping stem cells strong: RNA molecule protects stem cells during inflammation

Durham, NC (PRWEB) May 21, 2013

A new study appearing in the current issue of STEM CELLS Translational Medicine indicates that stem cells harvested from fat (adipose) are more potent than those collected from bone marrow in helping to modulate the bodys immune system.

The finding could have significant implications in developing new stem-cell-based therapies, as adipose tissue-derived stem cells (AT-SCs) are far more plentiful in the body than those found in bone marrow and can be collected from waste material from liposuction procedures. Stem cells are considered potential therapies for a range of conditions, from enhancing skin graft survival to treating inflammatory bowel disease.

Researchers at the Leiden University Medical Centers Department of Immunohematology and Blood Transfusion in Leiden, The Netherlands, led by Helene Roelofs, Ph.D., conducted the study. They were seeking an alternative to bone marrow for stem cell therapies because of the low number of stem cells available in marrow and also because harvesting them involves an invasive procedure.

Adipose tissue is an interesting alternative since it contains approximately a 500-fold higher frequency of stem cells and tissue collection is simple, Dr. Roelofs said.

Moreover, Dr. Melief added, 400,000 liposuctions a year are performed in the U.S. alone, where the aspirated adipose tissue is regarded as waste and could be collected without any additional burden or risk for the donor.

For the study, the team used stem cells collected from the bone marrow and fat tissue of age-matched donors. They compared the cells ability to regulate the immune system in vitro and found that the two performed similarly, although it took a smaller dose for the AT-SCs to achieve the same effect on the immune cells.

When it came to secreting cytokines the cell signaling molecules that regulate the immune system the AT-SCs also outperformed the bone marrow-derived cells.

This all adds up to make AT-SC a good alternative to bone marrow stem cells for developing new therapies, Dr. Roelofs concluded.

Cells from bone marrow and from fat were equivalent in terms of their potential to differentiate into multiple cell types, said Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of Wake Forest Institute for Regenerative Medicine. The fact that the cells from fat tissue seem to be more potent at suppressing the immune system suggest their promise in clinical therapies.

Originally posted here:
Stem Cells from Fat Outperform Those from Bone Marrow in Fighting Disease

Public release date: 21-May-2013 [ | E-mail | Share ]

Contact: Deborah Williams-Hedges debwms@caltech.edu 626-395-3227 California Institute of Technology

When infections occur in the body, stem cells in the blood often jump into action by multiplying and differentiating into mature immune cells that can fight off illness. But repeated infections and inflammation can deplete these cell populations, potentially leading to the development of serious blood conditions such as cancer. Now, a team of researchers led by biologists at the California Institute of Technology (Caltech) has found that, in mouse models, the molecule microRNA-146a (miR-146a) acts as a critical regulator and protector of blood-forming stem cells (called hematopoietic stem cells, or HSCs) during chronic inflammation, suggesting that a deficiency of miR-146a may be one important cause of blood cancers and bone marrow failure.

The team came to this conclusion by developing a mouse model that lacks miR-146a. RNA is a polymer structured like DNA, the chemical that makes up our genes. MicroRNAs, as the name implies, are a class of very short RNAs that can interfere with or regulate the activities of particular genes. When subjected to a state of chronic inflammation, mice lacking miR-146a showed a decline in the overall number and quality of their HSCs; normal mice producing the molecule, in contrast, were better able to maintain their levels of HSCs despite long-term inflammation. The researchers' findings are outlined in the May 21 issue of the new journal eLIFE.

"This mouse with genetic deletion of miR-146a is a wonderful model with which to understand chronic-inflammation-driven tumor formation and hematopoietic stem cell biology during chronic inflammation," says Jimmy Zhao, the lead author of the study and a MD/PhD student in the Caltech laboratory of David Baltimore, the Robert Andrews Millikan Professor of Biology. "It was surprising that a single microRNA plays such a crucial role. Deleting it produced a profound and dramatic pathology, which clearly highlights the critical and indispensable function of miR-146a in guarding the quality and longevity of HSCs."

The study findings provide, for the first time, a detailed molecular connection between chronic inflammation, and bone marrow failure and diseases of the blood. These findings could lead to the discovery and development of anti-inflammatory molecules that could be used as therapeutics for blood diseases. In fact, the researchers believe that miR-146a itself may ultimately become a very effective anti-inflammatory molecule, once RNA molecules or mimetics can be delivered more efficiently to the cells of interest.

The new mouse model, Zhao says, also mimics important aspects of human myelodysplastic syndrome (MDS)a form of pre-leukemia that often causes severe anemia, can require frequent blood transfusions, and usually leads to acute myeloid leukemia. Further study of the model could lead to a better understanding of the condition and therefore potential new treatments for MDS.

"This study speaks to the importance of keeping chronic inflammation in check and provides a good rationale for broad use of safer and more effective anti-inflammatory molecules," says Baltimore, who is a coauthor of the study. "If we can understand what cell types and proteins are critically important in chronic-inflammation-driven tumor formation and stem cell exhaustion, we can potentially design better and safer drugs to intervene."

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Funding for the research outlined in the eLIFE paper, titled "MicroRNA-146a acts as a guardian of the quality and longevity of hematopoietic stem cells in mice," was provided by the National Institute of Allergy and Infectious Disease; the National Heart, Lung, and Blood Institute; and the National Cancer Institute. Yvette Garcia-Flores, the lead technician in Baltimore's lab, also contributed to the study along with Dinesh Rao from UCLA and Ryan O'Connell from the University of Utah. eLIFE, a new open-access, high-impact journal, is backed by three of the world's leading funding agencies, the Howard Hughes Medical Institute, the Max Planck Society, and the Wellcome Trust.

Original post:
Keeping stem cells strong

The news of another breakthrough in Oregon in stem-cell technology the cloning of embryos using human tissues and then the ability to harvest stem cells from them opens up new possibilities in the personalisation of therapeutic cloning. But, closer to home, it serves to draw attention once again to the lacunae in Irish law that have left most of a field of fast-developing research and the whole area of assisted reproduction unregulated, Irish scientists unable to pursue cutting edge science, funding withheld, and potential patients vulnerable to unscrupulous scientists.

Ironically the breakthrough comes as our legislators battle with abortion legislation. Both issues, tied up as they are with thorny ethical issues around where life begins and when and how embryos acquire rights, are equally politically toxic. Both have also been the subject of urgent injunctions from the frustrated courts to politicians to fulfil their responsibility to legislate. Both, crucially, also require a willingness and courage on the part of politicians to move beyond absolutist moral positions to a new legislative ethics based on pluralist values and real social needs .

Having grasped one nettle, abortion legislation, is it too much to ask our politicians to do the same with bioethics stem cell research and provision for assisted reproduction, specifically in-vitro fertilisation (IVF)? Two reports, from the Government- appointed Commission on Assisted Human Reproduction and from the Irish Council for Bioethics, the first going back to 2005, proposed practical, conservative, guidelines for legislation that respect most of the sensitivities around ethical concerns over the production of embryos for research purposes. Crucially, they would limit researchers to using embryos that are surplus to requirements in the IVF process and which would otherwise be discarded/destroyed.

In the interim the Supreme Court in Roche v Roche (2009) has facilitated such legislation by clarifying the point at which it views the foetus as acquiring constitutional protection implantation in the womb. Any earlier and embryonic stem cell research, IVF, and contraceptives based on preventing implantation, including the day-after pill, would have been prohibited. Of course, the absence of a constitutional protection for the early embryo does not mean an easy consensus will be reached. As the abortion debate has shown, many are only too willing to challenge and flatly deny the courts interpretations, but its thoughtful ruling in Roche can provide a coherent rationale for the emerging middle ground of legislators and for carefully limited legislative provision for stem cell research and assisted reproduction.

It understood that legislation is currently being drafted by the Department of Health. It is now long overdue.

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Time to legislate on stem cells

Javascript is currently disabled in your web browser. For full site functionality, it is necessary to enable Javascript. In order to enable it, please see these instructions. 11 hours ago by Merlin Crossley, The Conversation Credit: euthman

In a paper published in Cell yesterday, scientists from the US and Thailand have, for the first time, successfully produced embryonic stem cells from human skin cells.

That sounds interesting, but what are stem cells and where do they come from?

If you take a limb from a rose tree, and put it in soil, it will grow into a thriving bush.

But you might say: "Plants are special. This won't work with animals." Or will it? If you cut off a lizard's tail, a new tail may grow. A lobster can grow back a lost claw.

There is a special type of flatworm that can be cut in half, again and again hundreds of times, and each half grows back into a full worm.

Similarly, if you cut out half a human liver, it will grow back. The story of Prometheus, whose liver was eaten away by eagles and regrew each day, suggests that the Greeks of ancient times knew about regeneration of organs.

This sort of regeneration is attributed to special cells called "stem cells".

Reprogramming the workers

Most of our cells are like many professional workers they are hardened in their ways and can't manage career changes.

See the original post:
Explainer: What are stem cells?

Newswise The Stem Cell Research Italy Association (www.stemcellitaly.org) and the Sbarro Health Research Organization (www.shro.org) make a public plea for a correct use of stem cell therapy in Italy and Europe.

Stem Cell Research Italy (SCR Italy) strongly endorses the point of view of eminent scientists who published a commentary on the regulation of stem cell therapy in Europe (Bianco et al Regulation of stem cell therapies under attack in Europe: for whom the bell tolls EMBO J. 2013 May 3. doi: 10.1038/emboj.2013.114).

In the present plea SCR quotes the hot topic issues that were addressed in the commentary.

The Italian Parliament is debating a new law that would make it legal to practice an unproven stem cell treatment in public hospitals. The treatment, offered by a private non-medical organization, may not be safe, lacks a rationale, and violates current national laws and European regulations. This case raises multiple concerns, most prominently the urgent need to protect patients who are severely ill, exposed to significant risks, and vulnerable to exploitation.

It must be underlined that stem cells are not a homogeneous class of cells; stem cells are not one-size-fits-all cures. There are different kinds of stem cells in different tissues, and even when the appropriate stem cell is selected for an indication it takes years of research to learn how to administer the stem cell safely and effectively.

Empiricism as a productive approach in medicine is often invoked as a reason to conduct trials with stem cells, blind of any putative mechanism of action.

Conducting formal, regulated, transparent clinical trials using stem cells can be legitimate, even if based on a partial or weak rationale. It is also, however, expensive and highly likely to be uninformative. Scientific approach must be robust before one embarks on a clinical trial. Mechanistic insight is not a dispensable intellectual luxury. It is specifically required to develop effective therapies. It is to this end that we need mechanisms and rationale.

A model of translational medicine has been subliminally accepted by many scientists. The scheme is driven by the pressure to effect the rapid translation of data from the bench. Premature translation of provisional data and concepts in the stem cell field, in conjunction with loosened regulation, can perhaps bring to the market products, but cannot provide solutions for diseases.

On this premise, scientists must clearly inform public opinion and authorities on the potential risks of stem cell therapy to avoid media campaign vowing the right of sick people to have access stem cell therapy for compassionate use. It has to be firmly rejected the argument offered by media and public opinion of a compassionate use of stem cells: there is no compassion without safety and efficacy. Exposing the weakest people to unknown risks is ethically unacceptable. Recourse to unproven and unsafe therapy is said to be compassion, or to fall into an arbitrary category of compassionate treatment. This is not the case at all. Compassion only applies when one offers a safe and potentially effective remedy. That a remedy is effective must be supported by published clinical data. If such data are not available, there is no legitimate assumption of effectiveness in the individual patient, and therefore no compassion.

In conclusion SCR Italy strongly agree with the notion that only rigorous science and rigorous regulation can ensure translation of science into effective therapies rather than into ineffective market products, and mark, at the same time, the sharp distinction between the striving for new therapies and the deceit of patients.

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Plea for a Correct Use of Stem Cells in Therapy

NEW YORK, N.Y. - Scientists have finally recovered stem cells from cloned human embryos, a longstanding goal that could lead to new treatments for such illnesses as Parkinson's disease and diabetes.

A prominent expert called the work a landmark, but noted that a different, simpler technique now under development may prove more useful.

Stem cells can turn into any cell of the body, so scientists are interested in using them to create tissue for treating disease. Transplanting brain tissue might treat Parkinson's disorder, for example, and pancreatic tissue might be used for diabetes.

But transplants run the risk of rejection, so more than a decade ago, researchers proposed a way around that: Create tissue from stem cells that bear the patient's own DNA, obtained with a process called therapeutic cloning.

If DNA from a patient is put into a human egg, which is then grown into an early embryo, the stem cells from that embryo would provide a virtual genetic match. So in theory, tissues created from them would not be rejected by the patient.

That idea was met with some ethical objections because harvesting the stem cells involved destroying human embryos.

Scientists have tried to get stem cells from cloned human embryos for about a decade, but they've failed. Generally, that's because the embryos stopped developing before producing the cells. In 2004, a South Korean scientist claimed to have gotten stem cells from cloned human embryos, but that turned out to be a fraud.

In Wednesday's edition of the journal Cell, however, scientists in Oregon report harvesting stem cells from six embryos created from donated eggs. Two embryos had been given DNA from skin cells of a child with a genetic disorder, and the others had DNA from fetal skin cells.

Shoukhrat Mitalipov of the Oregon Health & Science University, who led the research, said the success came not from a single technical innovation, but from revising a series of steps in the process. He noted it had taken six years to reach the goal after doing it with monkey embryos.

Mitalipov also said that based on monkey work, he believes human embryos made with the technique could not develop into cloned babies, and he has no interest in trying to do that. Scientists have cloned more than a dozen kinds of mammals, starting with Dolly the sheep.

The rest is here:
US scientists finally get stem cells from cloned human embryos, possible step to treatments