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Muscle Repair Potential Discovered in Human Source of Adult Stem Cells

Science Daily, September 5, 2007

With the potential to treat muscle injuries and diseases such as muscular dystrophy and heart attack, scientists at Children's Hospital of Pittsburgh of UPMC have discovered a unique population of adult stem cells derived from human muscle that can be used for this purpose for the first time.

Led by Johnny Huard, PhD, and Bruno Péault, PhD, a study at the Children's Stem Cell Research Center has isolated and characterized stem cells taken from blood vessels (known as myoendothelial cells). The cells were determined to be capable of proliferating into cartilage, bone and muscle tissue. The study was conducted using human muscle tissue and the cells were easily isolated using cell-sorting techniques.

According to Drs. Huard and Péault, the cells are ideally suited as a potential therapy for muscle injuries and diseases because of these characteristics.

"Finding this population of stem cells in a human source represents a major breakthrough for us because it brings us much closer to a clinical application of this therapy," said Dr. Huard, the Henry J. Mankin Professor and vice chair for Research in the Department of Orthopaedic Surgery at the University of Pittsburgh School of Medicine.

"To make this available as a therapy, we would take a muscle biopsy from a patient with a muscle injury or disease, remove the myoendothelial cells and treat the cells in the lab. The stem cells would then be re-injected into the patient to repair the muscle damage. Because this is an autologous transplant, meaning from the patient to himself, there is not the risk of rejection you would have if you took the stem cells from another source."

Dr. Huard's laboratory team first identified a unique population of muscle-derived stem cells with the ability to repair muscle 8 years ago while working with dystrophic mice in the process of searching for a cure for Duchenne muscular dystrophy (DMD).

The importance of determining the origin of these muscle-derived stem cells was recognized by Dr. Péault, who is a professor in the Department of Pediatrics, Cell Biology and Physiology at the University of Pittsburgh School of Medicine. It was discovered that these myoendothelial cells are located adjacent to the walls of blood vessels during human muscle biopsies using techniques of confocal microscopy and cell sorting by flow cytometry among others.

Opposed to other sources of stem cells known as satellite and endothelial cells, myoendothelial cells taken from the blood vessels are much more efficient at forming muscle according to the study.

A concern with other stem cell therapies, myoendothelial cells also showed no propensity to form tumors. And compared with 9 and 5 muscle fibers for endothelial and satellite cells, respectively; a thousand myoendothelial cells transplanted into the injured skeletal muscle of immunodeficient mice produced, on average, 89 muscle fibers.

Numerous therapeutic uses for the population of stem cells the SCRC team identified are being developed and researched by Drs. Huard, Péault and colleagues in Children's Stem Cell Research Center (SCRC). Affecting an estimated 3,500 boys, DMD, which is a genetic disease, could be one of hte most promising application targets of the treatment. Patients with DMD lack dystrophin, a protein that gives muscle cells structure.

In order to treat a variety of orthopedic and musculoskeletal diseases and injuries, Dr. Huard is an internationally recognized cell biologist conducting laboratory research into the therapeutic use of stem cells. To repair damaged muscle and regenerate bone and cartilage, Dr. Huard is developing cutting-edge therapies in the lab. The repair of sports-related bone, cartilage and muscle injuries to the repair of heart muscle damaged by heart attack could be among the range of applications the therapies could be used to treat.

Dr. Péault's laboratory has also deciphered the ultimate origin during embryonic life while becoming internationally recognized principally for their work on the prospective identification and characterization of human hematopoietic (blood) stem cells. Elusive populations of multipotent stem cells that persist in adult tissues, including dispensable ones like fat, are also being investigated by the team aside from blood development. Patients suffering from multiple organs damaged by acquired diseases, genetic diseases, aging, or trauma should be greatly aided by regenerative therapies using such cells.

The journal Nature Biotechnology has published the results of the study in their September issue.


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