Monthly Archives: February 2014

Deep TCR Sequencing Reveals Extensive Renewal of the T Cell Repertoire Following Autologous Stem Cell Transplant in …

Posted: February 18, 2014 at 11:40 am

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Newswise WA, Seattle (February 17, 2014) A new study describes the complexity of the new T cell repertoire following immune-depleting therapy to treat multiple sclerosis, improving our understanding of immune tolerance and clinical outcomes.

In the Immune Tolerance Networks (ITN) HALT-MS study, 24 patients with relapsing, remitting multiple sclerosis received high-dose immunosuppression followed by a transplant of their own stem cells, called an autologous stem cell transplant, to potentially reprogram the immune system so that it stops attacking the brain and spinal cord. Data published today in the Journal of Clinical Investigation (http://www.jci.org/articles/view/71691?key=b64763243f594bab6646) quantified and characterized T cell populations following this aggressive regimen to understand how the reconstituting immune system is related to patient outcomes.

ITN investigators used a high-throughput, deep-sequencing technology (Adaptive Biotechnologies, ImmunoSEQTM Platform) to analyze the T cell receptor (TCR) sequences in CD4+ and CD8+ cells to compare the repertoire at baseline pre-transplant, two months post-transplant and 12 months post-transplant.

Using this approach, alongside conventional flow cytometry, the investigators found that CD4+ and CD8+ lymphocytes exhibit different reconstitution patterns following transplantation. The scientists observed that the dominant CD8+ T cell clones present at baseline were expanded at 12 months post-transplant, suggesting these clones were not effectively eradicated during treatment. In contrast, the dominant CD4+ T cell clones present at baseline were undetectable at 12 months, and the reconstituted CD4+ T cell repertoire was predominantly comprised of new clones.

The results also suggest the possibility that differences in repertoire diversity early in the reconstitution process might be associated with clinical outcomes. Nineteen patients who responded to treatment had a more diverse repertoire two months following transplant compared to four patients who did not respond. Despite the low number of non-responders, these comparisons approached statistical significance and point to the possibility that complexity in the T cell compartment may be important for establishing immune tolerance.

This is one of the first studies to quantitatively compare the baseline T cell repertoire with the reconstituted repertoire following autologous stem cell transplant, and provides a previously unseen in-depth analysis of how the immune system reconstitutes itself following immune-depleting therapy.

About The Immune Tolerance Network The Immune Tolerance Network (ITN) is a research consortium sponsored by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. The ITN develops and conducts clinical and mechanistic studies of immune tolerance therapies designed to prevent disease-causing immune responses, without compromising the natural protective properties of the immune system. Visit http://www.immunetolerance.org for more information.

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Scientists Get Closer to Rejuvenating Aging Muscles

Posted: February 17, 2014 at 11:49 pm

Posted: Monday, February 17, 2014, 7:00 AM

SUNDAY, Feb. 16, 2014 (HealthDay News) -- As millions of aging Baby Boomers know, muscle tone and strength declines with advancing age, regardless of gym workouts. Now scientists say they might have uncovered a clue as to why that happens -- and new cell targets to help reverse it.

In studies in aging mice, researchers at Stanford University found that, over time, the stem cells that help repair damaged muscle cells after injury are less able to do so.

This helps explain why regaining strength and recovering from a muscle injury gets more difficult with age, the researchers said in work published online Feb. 16 in the journal Nature Medicine.

"In the past, it's been thought that muscle stem cells themselves don't change with age, and that any loss of function is primarily due to external factors in the cells' environment," study senior author Helen Blau, director of Stanford's Baxter Laboratory for Stem Cell Biology, said in a university news release.

"However, when we isolated stem cells from older mice, we found that they exhibit profound changes with age," said Blau, a professor of microbiology and immunology at the university. "Two-thirds of the cells are dysfunctional when compared to those from younger mice, and the defect persists even when transplanted into young muscles."

The research also revealed, however, that there is a defect specific to old muscle stem cells that can be corrected, allowing scientists to rejuvenate the cells.

"Most exciting is that we also discovered a way to overcome the defect," Blau said. "As a result, we have a new therapeutic target that could one day be used to help elderly human patients repair muscle damage."

The muscle stem cells in 2-year-old mice are the equivalent of those found in 80-years-old humans. In conducting the study, the researchers found that many muscle stem cells from these mice had increased activity in a certain biological pathway that interferes with the production of the stem cells.

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Extensive renewal of the T cell repertoire following autologous stem cell transplant in MS

Posted: February 17, 2014 at 11:49 pm

PUBLIC RELEASE DATE:

17-Feb-2014

Contact: Philip Bernstein, Ph.D. ITNCommunications@immunetolerance.org 240-235-6132 Immune Tolerance Network

WA, Seattle (February 17, 2014) A new study describes the complexity of the new T cell repertoire following immune-depleting therapy to treat multiple sclerosis, improving our understanding of immune tolerance and clinical outcomes.

In the Immune Tolerance Network's (ITN) HALT-MS study, 24 patients with relapsing, remitting multiple sclerosis received high-dose immunosuppression followed by a transplant of their own stem cells, called an autologous stem cell transplant, to potentially reprogram the immune system so that it stops attacking the brain and spinal cord. Data published today in the Journal of Clinical Investigation quantified and characterized T cell populations following this aggressive regimen to understand how the reconstituting immune system is related to patient outcomes.

ITN investigators used a high-throughput, deep-sequencing technology (Adaptive Biotechnologies, ImmunoSEQTM Platform) to analyze the T cell receptor (TCR) sequences in CD4+ and CD8+ cells to compare the repertoire at baseline pre-transplant, two months post-transplant and 12 months post-transplant.

Using this approach, alongside conventional flow cytometry, the investigators found that CD4+ and CD8+ lymphocytes exhibit different reconstitution patterns following transplantation. The scientists observed that the dominant CD8+ T cell clones present at baseline were expanded at 12 months post-transplant, suggesting these clones were not effectively eradicated during treatment. In contrast, the dominant CD4+ T cell clones present at baseline were undetectable at 12 months, and the reconstituted CD4+ T cell repertoire was predominantly comprised of new clones.

The results also suggest the possibility that differences in repertoire diversity early in the reconstitution process might be associated with clinical outcomes. Nineteen patients who responded to treatment had a more diverse repertoire two months following transplant compared to four patients who did not respond. Despite the low number of non-responders, these comparisons approached statistical significance and point to the possibility that complexity in the T cell compartment may be important for establishing immune tolerance.

This is one of the first studies to quantitatively compare the baseline T cell repertoire with the reconstituted repertoire following autologous stem cell transplant, and provides a previously unseen in-depth analysis of how the immune system reconstitutes itself following immune-depleting therapy.

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Extensive renewal of the T cell repertoire following autologous stem cell transplant in MS

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Over 5,000 Cubans receive stem cell treatment: Expert

Posted: February 17, 2014 at 5:46 am

Havana, Feb 16 (IANS): More than 5,000 patients have received stem cell treatment in Cuba since its procedure was introduced in 2004, a medical expert said.

Porfirio Hernandez, researcher and vice director at the Hematology and Immunology Institute in Cuba, said the stem cell treatment method has been implemented in 13 of the 15 provinces in Cuba.

As a widely acknowledged pioneer of this practice, Hernandez said that more than 60 percent of patients receiving the treatment had suffered from severe ischemia at lower limbs and other blood vessel related ailments, reported Xinhua.

The therapy has also been used to reduce the sufferings of patients with severe orthopedic and cardiac problems, Hernandez added.

Stem cells are capable of self-renewing, regenerating tissues damaged by diverse disease, traumas, and ageing, and stimulating the creation of new blood vessels.

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Over 5,000 Cubans receive stem cell treatment: Expert

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CU-Boulder stem cell research may point to new ways of mitigating muscle loss

Posted: February 16, 2014 at 11:44 pm

PUBLIC RELEASE DATE:

16-Feb-2014

Contact: Bradley Olwin bradley.olwin@colorado.edu 303-492-6816 University of Colorado at Boulder

New findings on why skeletal muscle stem cells stop dividing and renewing muscle mass during aging points up a unique therapeutic opportunity for managing muscle-wasting conditions in humans, says a new University of Colorado Boulder study.

According to CU-Boulder Professor Bradley Olwin, the loss of skeletal muscle mass and function as we age can lead to sarcopenia, a debilitating muscle-wasting condition that generally hits the elderly hardest. The new study indicates that altering two particular cell-signaling pathways independently in aged mice enhances muscle stem cell renewal and improves muscle regeneration.

One cell-signaling pathway the team identified, known as p38 MAPK, appears to be a major player in making or breaking the skeletal muscle stem cell, or satellite cell, renewal process in adult mice, said Olwin of the molecular, cellular and developmental biology department. Hyperactivation of the p38 MAPK cell-signaling pathway inhibits the renewal of muscle stem cells in aged mice, perhaps because of cellular stress and inflammatory responses acquired during the aging process.

The researchers knew that obliterating the p38 MAPK pathway in the stem cells of adult mice would block the renewal of satellite cells, said Olwin. But when the team only partially shut down the activity in the cell-signaling pathway by using a specific chemical inhibitor, the adult satellite cells showed significant renewal, he said. "We showed that the level of signaling from this cellular pathway is very important to the renewal of the satellite cells in adult mice, which was a very big surprise," said Olwin.

A paper on the subject appeared online Feb. 16 in the journal Nature Medicine.

One reason the CU-Boulder study is important is that the results could lead to the use of low-dose inhibitors, perhaps anti-inflammatory compounds, to calm the activity in the p38 MAPK cell-signaling pathway in human muscle stem cells, said Olwin.

The CU-Boulder research team also identified a second cell-signaling pathway affecting skeletal muscle renewal a receptor known as the fibroblast growth factor receptor-1, or FGFR-1. The researchers showed when the FGFR-1 receptor protein was turned on in specially bred lab mice, the renewal of satellite cells increased significantly. "We still don't understand how that particular mechanism works," he said.

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CU-Boulder stem cell research may point to new ways of mitigating muscle loss

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CU-Boulder Stem Cell Research May Point to New Methods of Mitigating Muscle Loss

Posted: February 16, 2014 at 11:44 pm

Boulder, CO (PRWEB) February 16, 2014

New findings on why skeletal muscle stem cells stop dividing and renewing muscle mass during aging points up a unique therapeutic opportunity for managing muscle-wasting conditions in humans, says a new University of Colorado Boulder study.

According to CU-Boulder Professor Bradley Olwin, the loss of skeletal muscle mass and function as we age can lead to sarcopenia, a debilitating muscle-wasting condition that generally hits the elderly hardest. The new study indicates that altering two particular cell-signaling pathways independently in aged mice enhances muscle stem cell renewal and improves muscle regeneration.

One cell-signaling pathway the team identified, known as p38 MAPK, appears to be a major player in making or breaking the skeletal muscle stem cell, or satellite cell, renewal process in adult mice, said Olwin of the molecular, cellular and developmental biology department. Hyperactivation of the p38 MAPK cell-signaling pathway inhibits the renewal of muscle stem cells in aged mice, perhaps because of cellular stress and inflammatory responses acquired during the aging process.

The researchers knew that obliterating the p38 MAPK pathway in the stem cells of adult mice would block the renewal of satellite cells, said Olwin. But when the team only partially shut down the activity in the cell-signaling pathway by using a specific chemical inhibitor, the adult satellite cells showed significant renewal, he said. We showed that the level of signaling from this cellular pathway is very important to the renewal of the satellite cells in adult mice, which was a very big surprise, said Olwin.

A paper on the subject appeared online Feb. 16 in the journal Nature Medicine.

One reason the CU-Boulder study is important is that the results could lead to the use of low-dose inhibitors, perhaps anti-inflammatory compounds, to calm the activity in the p38 MAPK cell-signaling pathway in human muscle stem cells, said Olwin.

The CU-Boulder research team also identified a second cell-signaling pathway affecting skeletal muscle renewal a receptor known as the fibroblast growth factor receptor-1, or FGFR-1. The researchers showed when the FGFR-1 receptor protein was turned on in specially bred lab mice, the renewal of satellite cells increased significantly. We still dont understand how that particular mechanism works, he said.

Another major finding of the study was that while satellite cells transplanted from young mice to other young mice showed significant renewal for up to two years, those transplanted from old mice to young mice failed. We found definitively that satellite cells from an aged mouse are not able to maintain the ability to replenish themselves, Olwin said. This is likely one of the contributors to loss of muscle mass during the aging process of humans.

Co-authors included first author and CU-Boulder postdoctoral researcher Jennifer Bernet, former CU-Boulder graduate student John K. Hall, CU-Boulder undergraduate Thomas Carter, and CU-Boulder postdoctoral researchers Jason Doles and Kathleen Kelly-Tanaka. The National Institutes of Health and the Ellison Medical Foundation funded the study.

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Researchers rejuvenate stem cell population from elderly mice, enabling muscle recovery

Posted: February 16, 2014 at 11:41 pm

PUBLIC RELEASE DATE:

16-Feb-2014

Contact: Krista Conger kristac@stanford.edu 650-725-5371 Stanford University Medical Center

STANFORD, Calif. Researchers at the Stanford University School of Medicine have pinpointed why normal aging is accompanied by a diminished ability to regain strength and mobility after muscle injury: Over time, stem cells within muscle tissues dedicated to repairing damage become less able to generate new muscle fibers and struggle to self-renew.

"In the past, it's been thought that muscle stem cells themselves don't change with age, and that any loss of function is primarily due to external factors in the cells' environment," said Helen Blau, PhD, the Donald and Delia B. Baxter Foundation Professor. "However, when we isolated stem cells from older mice, we found that they exhibit profound changes with age. In fact, two-thirds of the cells are dysfunctional when compared to those from younger mice, and the defect persists even when transplanted into young muscles."

Blau and her colleagues also identified for the first time a process by which the older muscle stem cell populations can be rejuvenated to function like younger cells. "Our findings identify a defect inherent to old muscle stem cells," she said. "Most exciting is that we also discovered a way to overcome the defect. As a result, we have a new therapeutic target that could one day be used to help elderly human patients repair muscle damage."

Blau, a professor of microbiology and immunology and director of Stanford's Baxter Laboratory for Stem Cell Biology, is the senior author of a paper describing the research, which will be published online Feb. 16 in Nature Medicine. Postdoctoral scholar Benjamin Cosgrove, PhD, and former postdoctoral scholar Penney Gilbert, PhD, now an assistant professor at the University of Toronto, are the lead authors.

The researchers found that many muscle stem cells isolated from mice that were 2 years old, equivalent to about 80 years of human life, exhibited elevated levels of activity in a biological cascade called the p38 MAP kinase pathway. This pathway impedes the proliferation of the stem cells and encourages them to instead become non-stem, muscle progenitor cells. As a result, although many of the old stem cells divide in a dish, the resulting colonies are very small and do not contain many stem cells.

Using a drug to block this p38 MAP kinase pathway in old stem cells (while also growing them on a specialized matrix called hydrogel) allowed them to divide rapidly in the laboratory and make a large number of potent new stem cells that can robustly repair muscle damage, Blau said.

"Aging is a stochastic but cumulative process," Cosgrove said. "We've now shown that muscle stem cells progressively lose their stem cell function during aging. This treatment does not turn the clock back on dysfunctional stem cells in the aged population. Rather, it stimulates stem cells from old muscle tissues that are still functional to begin dividing and self-renew."

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adult stem cell therapy blood bone marrow astragalus herb benefits for rheumatoid arthritis – Video

Posted: February 16, 2014 at 11:40 pm


adult stem cell therapy blood bone marrow astragalus herb benefits for rheumatoid arthritis
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Pre-Leukemic Stem Cells Discovered by Canada Scientists to Prevent Blood Cancer – Video

Posted: February 16, 2014 at 9:42 pm


Pre-Leukemic Stem Cells Discovered by Canada Scientists to Prevent Blood Cancer
Canadian Researchers have Discovered a Pre-Leukemic Stem cell that may be at the Root of Acute Myeloid Leukemia and also be the "bad actor" that Evades Chemo...

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Pre-Leukemic Stem Cells Discovered by Canada Scientists to Prevent Blood Cancer - Video

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stem cell research stem cell therapy marrow transplant and lung repair stem cell transplant – Video

Posted: February 16, 2014 at 9:42 pm


stem cell research stem cell therapy marrow transplant and lung repair stem cell transplant
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stem cell research stem cell therapy marrow transplant and lung repair stem cell transplant - Video

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