Duke Team Turns Scar Tissue into Heart Muscle Without Using Stem Cells

By Duke Medicine News and Communications

Scientists at Duke University Medical Center have shown the ability to turn scar tissue that forms after a heart attack into heart muscle cells using a new process that eliminates the need for stem cell transplant.

The study, published online April 26 in the journal Circulation Research, used molecules called microRNAs to trigger the cardiac tissue conversion in a lab dish and, for the first time, in a living mouse, demonstrating the potential of a simpler process for tissue regeneration.

If additional studies confirm the approach in human cells, it could lead to a new way for treating many of the 23 million people worldwide who suffer heart failure, which is often caused by scar tissue that develops after a heart attack. The approach could also have benefit beyond heart disease.

"This is a significant finding with many therapeutic implications," said Victor J. Dzau, MD, a senior author on the study who is James B. Duke professor of medicine and chancellor of health affairs at Duke University. "If you can do this in the heart, you can do it in the brain, the kidneys, and other tissues. This is a whole new way of regenerating tissue."

To initiate the regeneration, Dzau's team at Duke used microRNAs, which are molecules that serve as master regulators controlling the activity of multiple genes. Tailored in a specific combination, the microRNAs were delivered into scar tissue cells called fibroblasts, which develop after a heart attack and impair the organ's ability to pump blood.

Once deployed, the microRNAs reprogrammed fibroblasts to become cells resembling the cardiomyocytes that make up heart muscle. The Duke team not only proved this concept in the laboratory, but also demonstrated that the cell conversion could occur inside the body of a mouse -- a major requirement for regenerative medicine to become a potential therapy.

"This is one of the exciting things about our study," said Maria Mirotsou, PhD, assistant professor of cardiology at Duke and a senior author of the study. "We were able to achieve this tissue conversion in the heart with these microRNAs, which may be more practical for direct delivery into cells and allow for possible development of therapies without using genetic methods or transplantation of stem cells."

The researchers said using microRNA for tissue regeneration has several potential advantages over genetic methods or transplantation of stem cells, which have been difficult to manage inside the body. Notably, the microRNA process eliminates technical problems such as genetic alterations, while also avoiding the ethical dilemmas posed by stem cells.

"It's an exciting stage for reprogramming science," said Tilanthi M. Jayawardena, PhD, first author of the study. "It's a very young field, and we're all learning what it means to switch a cell's fate. We believe we've uncovered a way for it to be done, and that it has a lot of potential."

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Duke Team Turns Scar Tissue into Heart Muscle Without Using Stem Cells

Division of Labor in Neural Stem Cell Maintenance

Newswise NEWARK, N.J. -- Sibling growth factors cooperate to maintain a pool of neuron-generating stem cells in the brain, according to a study published in the journal Stem Cells by researchers at the University of Medicine and Dentistry of New Jersey (UMDNJ).

Numerous soluble proteins and receptors help to maintain neural stem cells (NSCs) supportive environment in central nervous system (CNS). NSCs access some of these nurturing factors by sending cellular extensions into the cerebral spinal fluid (CSF), which is rich in stem cell-promoting proteins.

Insulin-like growth factors (IGF-I and IGF-II) are essential for the growth and development of the CNS. But although they are abundant in the brain and CSF, it was not clear whether they are required by NSCs. Steven Levison, PhD, and Teresa Wood, PhD, of UMDNJ-New Jersey Medical School and colleagues now show that IGF-I and II cooperate to maintain NSC numbers and the NSCs ability to self-renew. IGF-I maintains NSC numbers by promoting cell division (via the IGF-I receptor), whereas IGF-II drives the expression of proteins essential for NSC self-renewal and stemness (via the insulin receptor).

The role of IGF-I and -II in maintaining NSC numbers and function might help to explain the cognitive impairments associated with aging, as the abundance of both proteins declines with age.

Disclosure: This study was funded by a Deans grant from UMDNJ-New Jersey Medical School, NIH grants (R21HL094905, F31NS065607 and T32-HL069752) and a grant from the LeDucq Foundation.

The University of Medicine and Dentistry of New Jersey (UMDNJ) is New Jerseys only health sciences university with more than 6,000 students on five campuses attending the state's three medical schools, its only dental school, a graduate school of biomedical sciences, a school of health related professions, a school of nursing and New Jerseys only school of public health. UMDNJ operates University Hospital, a Level I Trauma Center in Newark, and University Behavioral HealthCare, which provides a continuum of healthcare services with multiple locations throughout the state.

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Division of Labor in Neural Stem Cell Maintenance

Hadassah centenary honored May 6 by Chicago chapter

By Natasha Wasinski Contributor April 23, 2012 11:10AM

Miriam Schencker Goldberger (right) sits with two of her four grandchildren, Ari Schencker, 7, and his sister Sadie, 9, as 4-year-old Noah Schencker approaches to have his photo taken. Miriam, a member to Hadassah for past 50 years, purchased life members

storyidforme: 29352286 tmspicid: 10613889 fileheaderid: 4867083

Updated: April 23, 2012 8:47PM

With this year marking its centennial anniversary, the largest Jewish membership and womens organization in the U.S. has much to celebrate.

The Chicago chapter of Hadassah, the Womens Zionist Organization of America, hosts a benefit dinner May 6 at the Bryn Mawr Country Club in Lincolnwood to support trailblazing stem cell research efforts of a Jerusalem medical center.

Special guest Ehud Kokia, director general of Hadassah University Medical Center, is visiting from Israel to give a keynote address.

He oversees the Hadassah organizations flagship cause, which includes two hospitals with 1,000 beds, 31 operating theaters, nine intensive care units and five medical-profession schools, owned and operated in collaboration with the Hebrew University.

Supporting health work is a core component of Hadassahs service-oriented mission.

The national volunteer-led organization provides funding for programs and projects in Israel related to the Hadassah Medical Organization, education and youth institutions, and reforestation and parks.

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Hadassah centenary honored May 6 by Chicago chapter

Hadassah centennial to be honored by Chicago chapter

By Natasha Wasinski Contributor April 23, 2012 11:10AM

Miriam Schencker Goldberger (right) sits with two of her four grandchildren, Ari Schencker, 7, and his sister Sadie, 9, as 4-year-old Noah Schencker approaches to have his photo taken. Miriam, a member to Hadassah for past 50 years, purchased life members

storyidforme: 29352286 tmspicid: 10613889 fileheaderid: 4867083

Updated: April 23, 2012 8:47PM

With this year marking its centennial anniversary, the largest Jewish membership and womens organization in the U.S. has much to celebrate.

The Chicago chapter of Hadassah, the Womens Zionist Organization of America, hosts a benefit dinner May 6 at the Bryn Mawr Country Club in Lincolnwood to support trailblazing stem cell research efforts of a Jerusalem medical center.

Special guest Ehud Kokia, director general of Hadassah University Medical Center, is visiting from Israel to give a keynote address.

He oversees the Hadassah organizations flagship cause, which includes two hospitals with 1,000 beds, 31 operating theaters, nine intensive care units and five medical-profession schools, owned and operated in collaboration with the Hebrew University.

Supporting health work is a core component of Hadassahs service-oriented mission.

The national volunteer-led organization provides funding for programs and projects in Israel related to the Hadassah Medical Organization, education and youth institutions, and reforestation and parks.

Read more from the original source:
Hadassah centennial to be honored by Chicago chapter

Hadassah centennial to be honored

By Natasha Wasinski Contributor April 23, 2012 8:14PM

Miriam Schencker Goldberger (right) sits with two of her four grandchildren, Ari Schencker, 7, and his sister Sadie, 9, as 4-year-old Noah Schencker approaches to have his photo taken. Miriam, a member to Hadassah for past 50 years, purchased life members

storyidforme: 29385357 tmspicid: 10613889 fileheaderid: 4867083

Updated: April 24, 2012 11:03AM

With this year marking its centennial anniversary, the largest Jewish membership and womens organization in the United States has much to celebrate.

The Chicago chapter of Hadassah, the Womens Zionist Organization of America, will conduct a benefit dinner May 6 at the Bryn Mawr Country Club in Lincolnwood to support stem-cell research efforts of a Jerusalem medical center.

Special guest Ehud Kokia, director general of Hadassah University Medical Center, is visiting from Israel to give a keynote address.

He oversees the Hadassah organizations flagship cause, which includes two hospitals with 1,000 beds, 31 operating theaters, nine intensive care units and five medical profession schools, owned and operated in collaboration with the Hebrew University.

Supporting health work is a core component of Hadassahs service-oriented mission.

The national volunteer-led organization provides funding for programs and projects in Israel related to the Hadassah Medical Organization, education and youth institutions, and reforestation and parks.

Originally posted here:
Hadassah centennial to be honored

Medical Center Researchers Discover "Housekeeping" Mechanism for Brain Stem Cells

Published: April 22, 2012

Findings offer new insights into neurologic development and regenerative therapies for neurologic disease

(New York, NY, April 22, 2012) Researchers at Columbia University Medical Center (CUMC) have identified a molecular pathway that controls the retention and release of the brains stem cells. The discovery offers new insights into normal and abnormal neurologic development and could eventually lead to regenerative therapies for neurologic disease and injury. The findings, from a collaborative effort of the laboratories of Drs. Anna Lasorella and Antonio Iavarone, were published today in the online edition of Nature Cell Biology.

The research builds on recent studies, which showed that stem cells reside in specialized niches, or microenvironments, that support and maintain them.

From this research, we knew that when stem cells detach from their niche, they lose their identity as stem cells and begin to differentiate into specific cell types, said co-senior author Antonio Iavarone, MD, professor of Pathology and Neurology at CUMC.

However, the pathways that regulate the interaction of stem cells with their niche were obscure, said co-senior author Anna Lasorella, MD, associate professor of Pathology and Pediatrics at CUMC and a member of the Columbia Stem Cell Initiative.

In the brain, the stem cell niche is located in an area adjacent to the ventricles, the fluid-filled spaces within the brain. Neural stem cells (NSCs) within the niche are carefully regulated, so that enough cells are released to populate specific brain areas, while a sufficient supply is kept in reserve.

Neural stem cells detaching from the vascular niche. Image credit: Anna Lasorella, CUMC /Nature Cell Biology

In previous studies, Drs. Iavarone and Lasorella focused on molecules called Id (inhibitor of differentiation) proteins, which regulate various stem cell properties. They undertook the present study to determine how Id proteins maintain stem cell identity.

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Medical Center Researchers Discover "Housekeeping" Mechanism for Brain Stem Cells

"Housekeeping" Mechanism for Brain Stem Cells Discovered

Findings offer new insights into neurologic development and regenerative therapies for neurologic disease

Newswise (New York, NY, April 22, 2012) Researchers at Columbia University Medical Center (CUMC) have identified a molecular pathway that controls the retention and release of the brains stem cells. The discovery offers new insights into normal and abnormal neurologic development and could eventually lead to regenerative therapies for neurologic disease and injury. The findings, from a collaborative effort of the laboratories of Drs. Anna Lasorella and Antonio Iavarone, were published today in the online edition of Nature Cell Biology.

The research builds on recent studies, which showed that stem cells reside in specialized niches, or microenvironments, that support and maintain them.

From this research, we knew that when stem cells detach from their niche, they lose their identity as stem cells and begin to differentiate into specific cell types, said co-senior author Antonio Iavarone, MD, professor of Pathology and Neurology at CUMC.

However, the pathways that regulate the interaction of stem cells with their niche were obscure, said co-senior author Anna Lasorella, MD, associate professor of Pathology and Pediatrics at CUMC and a member of the Columbia Stem Cell Initiative.

In the brain, the stem cell niche is located in an area adjacent to the ventricles, the fluid-filled spaces within the brain. Neural stem cells (NSCs) within the niche are carefully regulated, so that enough cells are released to populate specific brain areas, while a sufficient supply is kept in reserve.

In previous studies, Drs. Iavarone and Lasorella focused on molecules called Id (inhibitor of differentiation) proteins, which regulate various stem cell properties. They undertook the present study to determine how Id proteins maintain stem cell identity.

The team developed a genetically altered strain of mice in which Id proteins were silenced, or knocked down, in NSCs. In the absence of Id proteins, mice died within 24 hours of birth. Their brains showed markedly lowered NSC proliferative capacity, and their stem cell populations were reduced.

Studies of NSCs from this strain of mice revealed that Id proteins directly regulate the production of a protein called Rap1GAP, which in turn controls Rap1, one of the master regulators of cell adhesion. The researchers found that the Id-Rap1GAP-Rap1 pathway is critical for the adhesion of NSCs to their niche and for NSC maintenance. There may be other pathways involved, but we believe this is the key pathway, said Dr. Iavarone. There is good reason to believe that it operates in other kinds of stem cells, and our labs are investigating this question now.

This is a new idea, added Dr. Lasorella. Before this study, the prevailing wisdom was that NSCs are regulated by the niche components, conceivably through the release of chemical attractants such as cytokines. However, our findings suggest that stem cell identity relies on this mechanism.

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"Housekeeping" Mechanism for Brain Stem Cells Discovered

Treating cancer as a chronic disease?

ScienceDaily (Mar. 29, 2012) New research from the Technion-Israel Institute of Technology Rappaport Faculty of Medicine and Research Institute and the Rambam Medical Center may lead to the development of new methods for controlling the growth of cancer, and perhaps lead to treatments that will transform cancer from a lethal disease to a chronic, manageable one, similar to AIDS.

By placing cancer cells in and near a growth developed from a population of human stem cells, scientists have demonstrated that the cancer cells grow and proliferate more robustly when exposed to human cells than they do in a typical petri dish or mouse model. The cancer cell population is also more diverse than had previously been understood. The research was published in the current advanced online issue of the journal Stem Cells. Maty Tzukerman, Rambam senior research scientist and the project leader and senior co-author on the report, says that this model will facilitate targeted drug discovery aimed at blocking the cancer cell self-renewal process.

Previous studies have determined that some tumor cells appear to be differentiated, while others retain the self-renewal property that makes cancer so deadly. According to Technion Professor Karl Skorecki, director of Medical Research and Development at Rambam Health Care Campus and senior co-author on the report, this new research attempts to understand how cancer grows, and to find ways to halt the runaway replication.

In order to mimic the human cancer environment as closely as possible, the research team developed a teratoma -- a tumor made of a heterogenous mix of cells and tissues -- by enabling the differentiation of human embryonic stem cells into a variety of normally occurring human cell lines on a carrier mouse. The human cellular teratoma constitutes a new platform of healthy human cells for monitoring the behavior and proliferation of human cancer cells.

For this study, the team took cells from one woman's ovarian clear cell carcinoma and injected them either into or alongside the human stem cell-derived environment. "We noticed very early on, rather strikingly, that the human cancer cells grow more robustly when they are in the teratoma environment compared to any other means in which we grew them, such as in a mouse muscle or under the skin of a mouse," says Skorecki.

The scientists were able to tease out six different kinds of self-renewing cells, based on behavior -- how quickly they grow, how aggressive they are, how they differentiate -- and on their molecular profile. This was a previously unknown finding, that one tumor might have such a diversity of cells with crucial fundamental growth properties. Tzukerman explains that the growth of the cancer cell subpopulations can now be explained by their proximity to the human cell environment.

The researchers cloned and expanded the six distinct cell populations and injected them into the human stem cell teratomas. One key observation is that some cells, which were not self-replicating in any other model, became self-replicating when exposed to the human cells.

Skorecki said that while he wasn't surprised that the human environment affected the growth, he was in fact surprised by the magnitude of the effect: "We've known for years now that cancers are complex organs, but I didn't think the power of the human stem cell environment would be so robust, that it would make such a big difference in how the cells were grown."

The researchers point out that they do not yet know the cues that particularly enhance the cancer's proliferation, and the team is now working on isolating the factors from human cells that promote such plasticity and self-renewing properties. The scientists explain that this may eventually allow physicians to manage cancer as a chronic disease: instead of one therapy against the entire tumor, researchers may develop a method to tease out the variety of self-renewing cell lines of a particular tumor and determine what allows each to thrive, then attack that mechanism.

Skorecki and Tzukerman say that an important next step in this line of cancer research will be to identify and develop ways of blocking the factor or factors that promote this essential self-renewing property of cancer, thus relegating many forms of cancer to controllable, chronic diseases.

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Treating cancer as a chronic disease?

Newly identified stem cells may hold clues to colon cancer

Public release date: 29-Mar-2012 [ | E-mail | Share ]

Contact: Melissa Marino melissa.marino@vanderbilt.edu 615-322-4747 Vanderbilt University Medical Center

Vanderbilt-Ingram Cancer Center researchers have identified a new population of intestinal stem cells that may hold clues to the origin of colorectal cancer.

This new stem cell population, reported March 30 in the journal Cell, appears to be relatively quiescent (inactive) in contrast to the recent discovery of intestinal stem cells that multiply rapidly and is marked by a protein, Lrig1, that may act as a "brake" on cell growth and proliferation.

The researchers have also developed a new and clinically relevant mouse model of colorectal cancer that investigators can now use to better understand where and how the disease arises, as well as for probing new therapeutic targets.

Colorectal cancer is the second leading cause of cancer deaths in the United States. These tumors are thought to arise from a series of mutations in intestinal stem cells, which are long-lived, self-renewing cells that gives rise to all cell types in the intestinal tract.

For more than 30 years, scientists believed that intestinal stem cells were primarily quiescent, proliferating only rarely in order to protect the tissue against cancer. Then, in 2007, researchers reported finding a population of intestinal stem cells (marked by the molecule Lgr5) that were highly proliferative.

Those findings "really changed the way we think about intestinal stem cells," said Robert Coffey, Jr., M.D., Ingram Professor of Cancer Research, co-chair of Vanderbilt's Epithelial Biology Center and senior author on the study.

"It came to so dominate the field that it raised the question about whether quiescent stem cells even existand that's where we enter into the picture."

Coffey's lab studies the epidermal growth factor (EGF) signaling pathway which includes a family of receptors known as ErbBs and its role in cancers of epithelial tissues, like the intestinal tract.

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Newly identified stem cells may hold clues to colon cancer

Antibody Shrinks Tumors Of Seven Cancers

Featured Article Academic Journal Main Category: Cancer / Oncology Also Included In: Immune System / Vaccines;Stem Cell Research Article Date: 28 Mar 2012 - 2:00 PDT

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Senior author Dr Irving Weissman, professor of pathology at Stanford, and colleagues, write about their success in treating bladder, brain, breast, colon, liver, ovarian, and prostate cancer tumors in this week's online ahead of print issue of the Proceedings of the National Academy of Sciences.

They say the antibody blocks a protein known as CD47, that sends "don't eat me" signals that cancer cells use to stop macrophages and other cells of the immune system from gobbling them up.

Anti-CD47 is the first antibody treatment to work against a variety of human solid tumors. The investigators said they are now eager to get started with phase 1 and phase 2 clinical trials in humans within the next two years.

The treatment also significantly reduced the ability of the tumors to spread (metastasize) to other parts of the mice's bodies, and in some cases, the animals appeared to be "cured".

Weissman, who directs the Institute of Stem Cell Biology and Regenerative Medicine and the Ludwig Center for Cancer Stem Cell Research and Medicine, both at Stanford, told the press their findings show "conclusively" that CD47 is a "a legitimate and promising target for human cancer therapy":

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Antibody Shrinks Tumors Of Seven Cancers