Category Archives: Stem Cells

Pigs Bladder Helps Patients #39; Stem Cells Grow Missing Muscles
The promise that stem cells may someday help regenerate damaged tissue seems to be close to fulfillment. Scientists at the University of Pittsburgh School of...

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Newswise KANSAS CITY, MO Adult organisms ranging from fruit flies to humans harbor adult stem cells, some of which renew themselves through cell division while others differentiate into the specialized cells needed to replace worn-out or damaged organs and tissues.

Understanding the molecular mechanisms that control the balance between self-renewal and differentiation in adult stem cells is an important foundation for developing therapies to regenerate diseased, injured or aged tissue.

In the current issue of the journal Nature, scientists at the Stowers Institute for Medical Research report that competition between two proteins, Bam and COP9, balances the self-renewal and differentiation functions of ovarian germline stem cells (GSCs) in fruit flies (Drosophila melanogaster).

Bam is the master differentiation factor in the Drosophila female GSC system, says Stowers Investigator Ting Xie, Ph.D., and senior author of the Nature paper. In order to carry out the switch from self-renewal to differentiation, Bam must inactivate the functions of self-renewing factors as well as activate the functions of differentiation factors.

Bam, which is encoded by the gene with the unusual name of bag-of-marbles, is expressed at high levels in differentiating cells and very low levels in GSCs of fruit flies.

Among the self-renewing factors targeted by Bam is the COP9 signalosome (CSN), an evolutionarily conserved, multi-functional complex that contains eight protein sub-units (CSN1 to CSN8). Xie and his collaborators discovered that Bam and the COP9 sub-unit known as CSN4 have opposite functions in regulating the fate of GSCs in female fruit flies.

Bam can switch COP9 function from self-renewal to differentiation by sequestering and antagonizing CSN4, Xie says. Bam directly binds to CSN4, preventing its association with the seven other COP9 components via protein competition, he adds. CSN4 is the only COP9 sub-unit that can interact with Bam.

This study has offered a novel way for Bam to carry out the switch from self-renewal to differentiation, says Xie, whose lab uses a combination of genetic, molecular, genomic and cell biological approaches to investigate GSCs as well as somatic stem cells of fruit flies.

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Stowers Researchers Reveal Molecular Competition Drives Adult Stem Cells to Specialize

PUBLIC RELEASE DATE:

6-Aug-2014

Contact: Robert Miranda cogcomm@aol.com Cell Transplantation Center of Excellence for Aging and Brain Repair

Putnam Valley, NY. (Aug. 6, 2014) Recent studies have shown that transplanting induced pluripotent stem cell-derived neural stem cells (iPS-NSCs) can promote functional recovery after spinal cord injury in rodents and non-human primates. However, a serious drawback to the transplantation of iPS-NSCs is the potential for tumor growth, or tumorogenesis, post-transplantation.

In an effort to better understand this risk and find ways to prevent it, a team of Japanese researchers has completed a study in which they transplanted a human glioblastoma cell line into the intact spinal columns of laboratory mice that were either immunodeficient or immunocompetent and treated with or without immunosuppresant drugs. Bioluminescent imaging was used to track the transplanted cells as they were manipulated by immunorejection.

The researchers found that the withdrawal of immunosuppressant drugs eliminated tumor growth and, in effect, created a 'safety lock' against tumor formation as an adverse outcome of cell transplantation. They also confirmed that withdrawal of immunosuppression led to rejection of tumors formed by transplantation of induced pluripotent stem cell derived neural stem/progenitor cells (iPS-NP/SCs).

Although the central nervous system has shown difficulty in regenerating after damage, transplanting neural stem/progenitor cells (NS/PCs) has shown promise. Yet the problem of tumorogenesis, and increases in teratomas and gliomas after transplantation has been a serious problem. However, this study provides a provisional link to immune therapy that accompanies cell transplantation and the possibility that inducing immunorejection may work to reduce the likelihood of tumorogenesis occurring.

"Our findings suggest that it is possible to induce immunorejection of any type of foreign-grafted tumor cells by immunomodulation," said study co-author Dr. Masaya Nakamura of the Keio University School of Medicine. "However, the tumorogenic mechanisms of induced pluripotent neural stem/progenitor cells (iPS-NS/PCs) are still to be elucidated, and there may be differences between iPS-NS/PCs derived tumors and glioblastoma arising from genetic mutations, abnormal epigenetic modifications and altered cell metabolisms."

The researchers concluded that their model might be a reliable tool to target human spinal cord tumors in preclinical studies and also useful for studying the therapeutic effect of anticancer drugs against malignant tumors.

"This study provides evidence that the use of, and subsequent removal of, immunosuppression can be used to modulate cell survival and potentially remove tumor formation by transplanted glioma cells and provides preliminary data that the same is true for iPS-NS/PCs." said Dr. Paul Sanberg, distinguished professor at the Center of Excellence for Aging and Brain Repair, University of South Florida. "Further study is required to determine if this technique could be used under all circumstances where transplantation of cells can result in tumor formation and its reliability in other organisms and paradigms."

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Researchers seek 'safety lock' against tumor growth after stem cell transplantation

19 hours ago A bam mutant fruit fly ovary, known as the germanium, contains only adult stem cell-like cells (red) and spherical spectrosome (green). The accumulation of only adult stem cell-like cells indicates a mutation in the master differentiation factor bam completely blocks germline stem cell lineage differentiation. Credit: Ting Xie, Ph.D., Stowers Institute for Medical Research

Adult organisms ranging from fruit flies to humans harbor adult stem cells, some of which renew themselves through cell division while others differentiate into the specialized cells needed to replace worn-out or damaged organs and tissues.

Understanding the molecular mechanisms that control the balance between self-renewal and differentiation in adult stem cells is an important foundation for developing therapies to regenerate diseased, injured or aged tissue.

In the current issue of the journal Nature, scientists at the Stowers Institute for Medical Research report that competition between two proteins, Bam and COP9, balances the self-renewal and differentiation functions of ovarian germline stem cells (GSCs) in fruit flies (Drosophila melanogaster).

"Bam is the master differentiation factor in the Drosophila female GSC system," says Stowers Investigator Ting Xie, Ph.D., and senior author of the Nature paper. "In order to carry out the switch from self-renewal to differentiation, Bam must inactivate the functions of self-renewing factors as well as activate the functions of differentiation factors."

Bam, which is encoded by the gene with the unusual name of bag-of-marbles, is expressed at high levels in differentiating cells and very low levels in GSCs of fruit flies.

Among the self-renewing factors targeted by Bam is the COP9 signalosome (CSN), an evolutionarily conserved, multi-functional complex that contains eight protein sub-units (CSN1 to CSN8). Xie and his collaborators discovered that Bam and the COP9 sub-unit known as CSN4 have opposite functions in regulating the fate of GSCs in female fruit flies.

Bam can switch COP9 function from self-renewal to differentiation by sequestering and antagonizing CSN4, Xie says. "Bam directly binds to CSN4, preventing its association with the seven other COP9 components via protein competition," he adds. CSN4 is the only COP9 sub-unit that can interact with Bam.

"This study has offered a novel way for Bam to carry out the switch from self-renewal to differentiation," says Xie, whose lab uses a combination of genetic, molecular, genomic and cell biological approaches to investigate GSCs as well as somatic stem cells of fruit flies.

In the Nature paper, Xie's lab also reports that CSN4 is the only one of the eight sub-units that is not involved in the regulation of GSC differentiation of female fruit flies. "One possible explanation for the opposite effects of CSN4 and the other CSN proteins is that the sequestration of CSN4 by Bam allows the other CSN proteins to have differentiation-promoting functions," he says.

Link:
Team reveals molecular competition drives adult stem cells to specialize

Adult organisms ranging from fruit flies to humans harbor adult stem cells, some of which renew themselves through cell division while others differentiate into the specialized cells needed to replace worn-out or damaged organs and tissues.

Understanding the molecular mechanisms that control the balance between self-renewal and differentiation in adult stem cells is an important foundation for developing therapies to regenerate diseased, injured or aged tissue.

In the current issue of the journal Nature, scientists at the Stowers Institute for Medical Research report that competition between two proteins, Bam and COP9, balances the self-renewal and differentiation functions of ovarian germline stem cells (GSCs) in fruit flies (Drosophila melanogaster).

"Bam is the master differentiation factor in the Drosophila female GSC system," says Stowers Investigator Ting Xie, Ph.D., and senior author of the Nature paper. "In order to carry out the switch from self-renewal to differentiation, Bam must inactivate the functions of self-renewing factors as well as activate the functions of differentiation factors."

Bam, which is encoded by the gene with the unusual name of bag-of-marbles, is expressed at high levels in differentiating cells and very low levels in GSCs of fruit flies.

Among the self-renewing factors targeted by Bam is the COP9 signalosome (CSN), an evolutionarily conserved, multi-functional complex that contains eight protein sub-units (CSN1 to CSN8). Xie and his collaborators discovered that Bam and the COP9 sub-unit known as CSN4 have opposite functions in regulating the fate of GSCs in female fruit flies.

Bam can switch COP9 function from self-renewal to differentiation by sequestering and antagonizing CSN4, Xie says. "Bam directly binds to CSN4, preventing its association with the seven other COP9 components via protein competition," he adds. CSN4 is the only COP9 sub-unit that can interact with Bam.

"This study has offered a novel way for Bam to carry out the switch from self-renewal to differentiation," says Xie, whose lab uses a combination of genetic, molecular, genomic and cell biological approaches to investigate GSCs as well as somatic stem cells of fruit flies.

In the Nature paper, Xie's lab also reports that CSN4 is the only one of the eight sub-units that is not involved in the regulation of GSC differentiation of female fruit flies. "One possible explanation for the opposite effects of CSN4 and the other CSN proteins is that the sequestration of CSN4 by Bam allows the other CSN proteins to have differentiation-promoting functions," he says.

"As a powerful model system for studying adult stem cells, Drosophila female GSCs have revealed many novel regulatory strategies which have been later confirmed to be generally true," adds Su Wang, a co-first author of the paper and also a graduate student in Department of Anatomy and Cell Biology at University of Kansas Medical Center.

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Molecular competition drives adult stem cells to specialize, study shows

News Desk

The Nation

Publication Date : 07-08-2014

Thai police probing case involving nine babies found in a condo

Following much-publicised case of the unauthorised surrogacy involving a Thai mother and an Australian couple, a raid by Thai police and soldiers at a Bangkok condominium found nine babies thought to have been fathered by a Japanese man.

Former Thai Social Development and Human Security Minister Paveen Hongsakul, who initiated the raid on Tuesday on Soi Lat Phrao 130, feared that in the worst-case scenario, this "surrogacy-for-hire" scam may be related to the potentially fatal extraction of foetal fluid to provide stem cells.

She also called on authorities to investigate a case involving a woman who said she was paid for surrogate pregnancy, but lost the baby seven months into her pregnancy. Pavena wants investigators to find out if the foetus's spinal fluid was extracted for use in stem cell treatments.

As for the nine babies found in the Lat Phrao condo, Pavena said most of them looked Caucasian, while only one had Asian features. The infants were between 15 and 50 days old.

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Surrogacy arrangements suspected of being used for stem cells

MONDAY, Aug. 4, 2014 (HealthDay News) -- Could stem cell injections help rejuvenate your face or body? Probably not, plastic surgery experts say, but ads for these types of bogus procedures abound on the Internet.

"Stem cells offer tremendous potential, but the marketplace is saturated with unsubstantiated and sometimes fraudulent claims that may place patients at risk," a team led by Dr. Michael Longaker, of Stanford University Medical Center, wrote in a review published in the August issue of Plastic and Reconstructive Surgery.

The experts say consumers need to be wary of advertisements promoting the benefits of "minimally invasive, stem cell-based rejuvenation procedures." Claims for stem cell procedures for facelifts, breast augmentation and vaginal rejuvenation are not only unsubstantiated, but also risky, Longaker's team said.

They note that, to date, the U.S. Food and Drug Administration has approved only one cosmetic stem cell procedure designed to treat fine facial wrinkles. And since that single procedure was approved, the product involved has been monitored extensively.

Overall, cosmetic stem cell procedures have not undergone significant scientific scrutiny, the Stanford team said. The risks associated with stem cell and tissue processing have not been closely examined. The effects of aging on stem cells are also not well established, the researchers explained.

To investigate concerning claims being made about cosmetic stem cell procedures, the researchers performed a basic Internet search. They found the most common result was "stem cell facelifts." Most of the procedures used stem cells isolated from fat but did not provide details on the quality of the stem cells.

More than 100 clinical trials are currently evaluating stem cells derived from fat, but few are focusing on cosmetic treatments. The researchers cautioned that the products used in these cosmetic procedures likely involves additional types of cells unless they utilized sophisticated cell-sorting techniques.

Many blood plasma-enriched "platelet protein treatments" are also incorrectly advertised as stem cell therapy, the study's authors noted.

Meanwhile, there is only minimal evidence that cosmetic stem cell procedures have any anti-aging effects, the researchers said. They warn that stem cell facelifts may actually be "lipo-filling" procedures -- fat injections with no prolonged anti-aging effect.

Although stem cells do hold potential for cosmetic procedures in years to come, today's advertising claims for these procedures are going beyond any scientific evidence on safety and effectiveness, the researchers conclude.

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Most Cosmetic Procedures Based on Stem Cells Are Bogus, Experts Say

05.08.2014 - (idw) Goethe-Universitt Frankfurt am Main

Only one out of every two adult patients survive acute myeloid leukaemia (AML). It is assumed that leukaemic stem cells, which cannot be completely eliminated during treatment, are the origin of relapse. Now a team of Frankfurt-based researchers has discovered, that these cells do have a weakness: 5-LO inhibitors eliminate cells in culture and mouse models. FRANKFURT. Despite improved therapy, only one out of every two adult patients survive acute myeloid leukaemia (AML). The mean survival time for this disease, which predominantly occurs in the elderly, is less than a year for patients over 65 years. It is assumed that leukaemic stem cells, which cannot be completely eliminated during treatment, are the origin of relapse. However, as has been discovered by a team of Frankfurt-based researchers, these cells do have a weakness: In the current edition of the high impact journal "Cancer Research", they report that the enzyme 5-lipoxygenase (5-LO) plays a significant role in the survival of leukaemic AML stem cells.

5-LO is known for its role in inflammatory diseases like asthma. A team led by Dr. Marin Ruthardt from the Haematology Department of the Medical Clinic II and Dr. Jessica Roos, Prof. Diester Steinhilber and Prof. Thorsten Jrgen Maier from the Institute for Pharmaceutical Chemistry showed that the leukaemic stem cells in a subgroup of AML could be selectively and efficiently attacked by 5-LO inhibitors. This was demonstrable in cell culture models as well as in leukaemia mouse models.

"These results provide the basis for the potential implementation of 5-LO-inhibitors as stem cell therapeutic agents for a sustained AML cure, although this must be investigated further in preclinical and clinical studies in humans," explains Dr. Ruthardt. "In addition, there are plans for further molecular biological studies with the objective of understanding exactly how the 5-LO inhibitors act on the leukaemic cells", Prof. Maier continued.

Information PD Dr. Martin Ruthardt, Haematology/Medical Clinic II, Tel. +49/ 69/63015338, email: ruthardt@em.uni-frankfurt.de or Prof. Dr. Thorsten Jrgen Maier, Institute for Pharmaceutical Chemistry, Riedberg Campus, Tel.: +49/69/7982-934, email: maier@pharmchem.uni-frankfurt.de.

The Goethe University is an institution with particularly strong research capabilities based in the European financial metropolis of Frankfurt. It celebrates its 100th year of existence in 2014. The university was founded in 1914 through private means from liberally-orientated citizens of Frankfurt and has devoted itself to fulfilling its motto "Science for the Society" in its research and teaching activity right up to the present day. Many of the founding donors were of Jewish origin. During the last 100 years, the pioneering services offered by the Goethe University have impacted the fields of social, societal and economic sciences, chemistry, quantum physics, neurological research and labour law. On January 1st, 2008, it achieved an exceptional degree of independence as it returned to its historical roots as a privately funded university. Today it is one of the ten universities that are most successful in obtaining external research funding and one of the three largest universities in Germany with centres of excellence in medicine, life sciences and humanities.

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Weakness of leukaemic stem cells discovered

The promise that stem cells may someday help regenerate damaged tissue seems to be close to fulfillment. Scientists at the University of Pittsburgh School of Medicine report that some of their severely injured patients grew new muscle tissue with the help of pigs bladders.

After a skiing accident in which he lost much of the muscle in his left calf, Nicholas Clark could no longer do many of his regular activities.

In addition to the muscle loss, I had a lot of nerve loss and blood vessel loss and other tissue loss in that leg. So, it really limited any activity," said Clark.

Skeletal muscles can regenerate after minor injuries with help from physical therapy, but if the loss is greater than 20 percent, the damage becomes permanent, says Doctor Stephen Badylak of the University of Pittsburgh School of Medicine.

You're left with this huge gap that just fills in with scar tissue," said Badylak.

Scientists have long known that stem cells, applied at the point of injury, can actually turn into new muscle cells. But they need some sort of structure - a matrix - to grow on.

Badylak's team created an extracellular matrix from a pigs bladder. They removed all traces of cells from the tissue, so that the recipients immune system would not reject it.

The extracellular matrix is the glue, if you will, that holds all of the cells in our body together," said Badylak.

The matrix is implanted at the injury site, and as it slowly degrades in recipients body it releases chemicals that attract stem cells. Physical therapy helps the stem cells understand that they need to form muscle tissue.

All five patients in Badylak's study had lost 60 to 90 percent of the affected muscle. Six months after the start of therapy, all have grown some new muscle, and three patients had dramatic improvement. Clark says he can ride his bike again and even jump rope.

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Pigs Bladder Helps Patients' Stem Cells Grow Missing Muscles

Date:

August 4, 2014

Source:

Goethe-Universitt Frankfurt am Main

Summary:

Despite improved therapy, only one out of every two adult patients survive acute myeloid leukemia (AML). The mean survival time for this disease, which predominantly occurs in the elderly, is less than a year for patients over 65 years. It is assumed that leukemic stem cells, which cannot be completely eliminated during treatment, are the origin of relapse. However, as has been recently discovered, these cells do have a weakness: the enzyme 5-lipoxygenase (5-LO) plays a significant role in the survival of leukaemic AML stem cells, it turns out.

Despite improved therapy, only one out of every two adult patients survive acute myeloid leukemia (AML). The mean survival time for this disease, which predominantly occurs in the elderly, is less than a year for patients over 65 years. It is assumed that leukaemic stem cells, which cannot be completely eliminated during treatment, are the origin of relapse. However, as has been discovered by a team of Frankfurt-based researchers, these cells do have a weakness: In the current edition of the high impact journal "Cancer Research," they report that the enzyme 5-lipoxygenase (5-LO) plays a significant role in the survival of leukaemic AML stem cells.

5-LO is known for its role in inflammatory diseases like asthma. A team led by Dr. Marin Ruthardt from the Haematology Department of the Medical Clinic II and Dr. Jessica Roos, Prof. Diester Steinhilber and Prof. Thorsten Jrgen Maier from the Institute for Pharmaceutical Chemistry showed that the leukaemic stem cells in a subgroup of AML could be selectively and efficiently attacked by 5-LO inhibitors. This was demonstrable in cell culture models as well as in leukemia mouse models.

"These results provide the basis for the potential implementation of 5-LO-inhibitors as stem cell therapeutic agents for a sustained AML cure, although this must be investigated further in preclinical and clinical studies in humans," explains Dr. Ruthardt. "In addition, there are plans for further molecular biological studies with the objective of understanding exactly how the 5-LO inhibitors act on the leukaemic cells." Prof. Maier continued.

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Weakness of leukemic stem cells discovered