Adult Stem Cells May Target and Repair Heart Attack Damage

A 41-site clinical trial, testing the restorative effect that adult bone marrow stem cells have on damaged or injured myocardium in heart attack patients, is being led at Wake Forest Baptist by Sanjay Gandhi, MD.

Phase I of the research study found that stem cells derived from bone marrow (mesenchymal stem cells) were safe for patients and may have the ability to limit scar formation, improve heart function and preserve tissue following a first heart attack.

Phase I was a multicenter study of 53 patients which demonstrated that the treatment was safe in adults, and those patients given this stem cell therapy actually experienced improvement in their overall ejection fraction. The earlier phase of the study showed that these mesenchymal stem cells could target the damaged myocardial tissue and initiate a process for recovery of heart muscle that could hopefully result in improvement of the overall heart.

Wake Forest is currently participating in a Phase II multicenter study investigating the efficacy of a one-time infusion of adult bone marrow stem cells in heart attack patients. Patients who experience a first time heart attack and undergo coronary angioplasty and stenting are eligible. Investigators are studying whether treatment with stem cells results in less heart muscle damage and improved heart function following a heart attack.

Wake Forest Baptist is the only trial site in North Carolina, South Carolina, Virginia and West Virginia.

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Umbilical Stem Cells May Help Recover Lost Vision for Those With Corneal Disease

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CINCINNATI—New research from the University of Cincinnati may help in the recovery of lost vision for patients with corneal scarring.

Winston Whei-Yang Kao, PhD, professor of ophthalmology, along with other researchers in UC’s ophthalmology department found that transplanting human umbilical mesenchymal stem cells into mouse models that lack the protein lumican restored the transparency of cloudy and thin corneas.

Mesenchymal stem cells are “multi-potent” stem cells that can differentiate into a variety of cell types.

These findings are being presented Dec. 8 in San Diego at the 49th Annual Meeting of the American Society of Cell Biology.

“Corneal transplantation is currently the only true cure for restoration of eyesight that may have been lost due to corneal scarring caused by infection, mechanical and chemical wounds and congenital defects of genetic mutations,” Kao says. “However, the number of donated corneas suitable for transplantation is decreasing as the number of individuals receiving refractive surgeries, like LASIK, increases.”

“Worldwide, there is a shortage of suitable corneas for transplantation, and at the present time, there is no effective alternative procedure besides corneal transplantation to treat corneal blindness,” he continues. “There is a large need to develop alternative treatment regimens, one of which may be the transplantation of mesenchymal stem cells.”

Researchers used mouse models that did not have the lumican gene, also known as lumican knock-out models. Lumican is a protein that controls the formation and maintenance of transparent corneas.

“Lumican knock-out models manifested thin and cloudy corneas,” he says. “Transplantation of the umbilical stem cells significantly improved transparency and increased corneal stromal thickness in these mice.”

In addition, Kao says, the umbilical mesenchymal stem cells survived in the mouse stroma (connective tissue) for more than three months with minimal or no rejection and became corneal cells, repairing lost functions caused by mutations.

“Our results suggest a potential treatment regimen for congenital and/or acquired corneal diseases,” he says, adding that the availability of human umbilical stem cells is almost unlimited. “These stem cells are easy to isolate and can be recovered quickly from storage when treating patients.

“These findings have the potential to create new and better treatments—and an improved quality of life—for patients with vision loss due to corneal injury.”

This study was funded by grants from the National Eye Institute, Research to Prevent Blindness and the Ohio Lions Eye Research Foundation.

from http://healthnews.uc.edu/news/?/9613/

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The Role of Hiwi in Stem Cell Maintenance and Sarcomagenesis

Sarcomas are cancers of connective tissues, such as bone, adipose and cartilage, and are thought to arise from the aberrant development of the mesenchyme. As such, mesenchymal stem cells are thought to be the cell of origin for sarcomas. Genetic or epigenetic lesions at particular points during the differentiation of a mesenchymal stem cell into its terminal mesenchymal cell type are able to give rise to specific subtypes of sarcomas.

Recently, a number of reports have identified elevated expression of the human Piwi homolog–called Hiwi–in a variety of human cancers, including gastric cancer, pancreatic cancer, gliomas and, most relevant for this dissertation, sarcomas. In sarcomas, Hiwi is highly expressed and elevated Hiwi prognosticates shorter patient survival. Hiwi is the human homolog of the Piwi family of proteins, which are members of the Paz-Piwi Doman (PPD) family.

During normal development, Piwis are thought to maintain stem cells of the germline, and indeed their expression is limited to early development and to the adult germline. Piwis are thought to maintain stem cells in the germline with small RNA partners, called piwi-interacting RNAs (piRNAs). More specifically, Piwi/piRNA complexes in the germline are thought to maintain transposon silencing, and thus ensure genomic stability.

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Promoting Healing by Keeping Skeletal Stem Cells ‘Young’

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Scientists seeking new ways to fight maladies ranging from arthritis and osteoporosis to broken bones that won’t heal have cleared a formidable hurdle, pinpointing and controlling a key molecular player to keep stem cells in a sort of extended infancy. It’s a step that makes treatment with the cells in the future more likely for patients.

Controlling and delaying development of the cells, known as mesenchymal (pronounced meh-ZINK-a-mill) stem cells, is a long-sought goal for researchers. It’s a necessary step for doctors who would like to expand the number of true skeletal stem cells available for a procedure before the cells start becoming specific types of cells that may – or may not – be needed in a patient with, say, weak bones from osteoporosis, or an old knee injury.

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First Stem Cell Drug Fails 2 Late-Stage Clinical Trials

What might become the first drug derived from human stem cells failed in two late-stage clinical trials, dealing a setback to the drug’s developer and to the stem cell field (…)

Prochymal is a preparation of mesenchymal stem cells, which are obtained from the bone marrow of healthy young adults.
Because the cells are derived from adults, they sidestep the ethical issues stemming from the destruction of human embryos needed to make embryonic stem cells. Unlike most other types of adult stem cells, mesenchymal cells grow well in culture, so thousands of doses can be produced from a single donation.

Stem cells, particularly in the form of bone marrow transplants, are already used in medicine. Osiris is hoping that Prochymal will become the first stem cell product approved by the Food and Drug Administration and sold as a mass-produced pharmaceutical product (…)

from http://www.nytimes.com/2009/09/09/health/research/09drug.html

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