Taking the Strain Off Injured Muscles

Newswise — Whether you pull a muscle playing backyard hoops or in the NBA playoffs, the pain can drag on for weeks. Inside the muscle, the damage caused by tears, bruises, strains, insufficient blood flow or nerve damage responds slowly to current therapies, none of which can guarantee complete muscle regeneration or 100 percent functional recovery. Even leading-edge medicines such as muscle growth factors can't reverse scar tissue formation, the result of the process of fibrosis.

The University of Pittsburgh laboratory of Johnny Huard has had some recent success in improving functional recovery of injured skeletal muscle, at least in mice, with the use of decorin, an anti-fibrosis agent. Yet scar tissue still formed in a time-dependent manner in injured mouse muscle, with the most serious fibrosis occurring four weeks after injury. In work presented at the American Society for Cell Biology's 43rd Annual Meeting in San Francisco, Huard's lab took a closer look at scar tissue formation by transplanting muscle-derived stem cells by injection into the skeletal muscles of mice. Four weeks after transplantation, the researchers surgically cut the injected muscles to create a model laceration injury. The injected stem cells, they discovered later, made the scarring worse by developing into fibrotic cells. Following up, the researchers repeated the experiment but concentrated on looking for high levels of growth factors in the injured skeletal muscle. Sure enough, they observed high levels of a protein called transforming growth factor TGF-beta1.

The researchers then delivered TGF-beta 1 DNA into mouse muscle cells growing in lab culture and into mouse muscle cells growing in live mice. The TGF-beta 1 induced both types to become fibrotic. Huard and colleagues now believe that TGF-beta1 triggers the pathological process of scar formation. To fully restore injured muscle, new therapies whether they use stem cells, growth factors or other agents, have to figure a way around TGF-beta1. Until then, sidelined weekend warriors or play-through-the-pain pros can only grin and bear it, in hopes of eventual recovery.

Scar Tissue Formation in Injured Skeletal Muscle, Yong Li 1,2, William Foster 1, Yisheng Chan 1,2, Ying Tan 1, and Johnny Huard 1,2,3. 1.Growth and Development Laboratory, Children's Hospital of Pittsburgh; 2. Department of Orthopaedic Surgery, University of Pittsburgh; 3. Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA 15213. Funding: This work is funded by the National Institutes of Health, 1 RO1 AR47973-02).