What if repairing large segments of damaged muscle tissue was as simple as mobilizing the body's stem cells to the site of the injury? New research in mice and rats, conducted at Wake Forest Baptist Medical Center's Institute for Regenerative Medicine, suggests that "in body" regeneration of muscle tissue might be possible by harnessing the body's natural healing powers.
Reporting online ahead of print in the journal Acta Biomaterialia, the research team demonstrated the ability to recruit stem cells that can form muscle tissue to a small piece of biomaterial, or scaffold that had been implanted in the animals' leg muscle. The secret to success was using proteins involved in cell communication and muscle formation to mobilize the cells.
"Working to leverage the body's own regenerative properties, we designed a muscle-specific scaffolding system that can actively participate in functional tissue regeneration," said Sang Jin Lee, Ph.D., assistant professor of regenerative medicine and senior author. "This is a proof-of-concept study that we hope can one day be applied to human patients."
The current treatment for restoring function when large segments of muscle are injured or removed during tumor surgery is to surgically move a segment of muscle from one part of the body to another. Of course, this reduces function at the donor site.
Several scientific teams are currently working to engineer replacement muscle in the lab by taking small biopsies of muscle tissue, expanding the cells in the lab, and placing them on scaffolds for later implantation. This approach requires a biopsy and the challenge of standardizing the cells.
"Our aim was to bypass the challenges of both of these techniques and to demonstrate the mobilization of muscle cells to a target-specific site for muscle regeneration," said Lee.
Most tissues in the body contain tissue-specific stem cells that are believed to be the "regenerative machinery" responsible for tissue maintenance. It was these cells, known as satellite or progenitor cells, that the scientists wanted to mobilize.
First, the Wake Forest Baptist scientists investigated whether muscle progenitor cells could be mobilized into an implanted scaffold, which basically serves as a "home" for the cells to grow and develop. Scaffolds were implanted in the lower leg muscle of rats and retrieved for examination after several weeks.
Lab testing revealed that the scaffolds contained muscle satellite cells as well as stem cells that could be differentiated into muscle cells in the lab. In addition, the scaffold had developed a network of blood vessels, with mature vessels forming four weeks after implantation.
Next, the scientists tested the effects of several proteins known to be involved in muscle formation by designing the scaffolds to release these proteins. The protein with the greatest effect on cell recruitment was insulin-like growth factor 1 (IGF-1).
After several weeks of implantation, lab testing showed that the scaffolds with IGF-1 had up to four times the number of cells than the plain scaffolds and also had increased formation of muscle fibers.
"The protein effectively promoted cell recruitment and accelerated muscle regeneration," said Lee.
Next, the scientists will evaluate whether the regenerated muscle is able to restore function and will test clinical feasibility in a large animal model.
The research was supported by the Armed Forces Institute of Regenerative Medicine, a federally funded effort to apply regenerative medicine to battlefield injuries.
Co-researchers were: Young Min Ju, Ph.D., lead author, Anthony Atala, M.D., and James J. Yoo, M.D., Ph.D., all with the Institute for Regenerative Medicine.
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Wake Forest Baptist Medical Center is a nationally recognized academic medical center in Winston-Salem, N.C., with an integrated enterprise including educational and research facilities, hospitals, clinics, diagnostic centers and other primary and specialty care facilities serving 24 counties in northwest North Carolina and southwest Virginia. Its divisions are Wake Forest Baptist Health, a regional clinical system with close to 175 locations, 900 physicians and 1,000 acute care beds; Wake Forest School of Medicine, an established leader in medical education and research; and Wake Forest Innovations, which promotes the commercialization of research discoveries and operates Wake Forest Innovation Quarter, an urban research and business park specializing in biotechnology, materials science and information technology. Wake Forest Baptist clinical, research and educational programs are annually ranked among the best in the country by U.S. News & World Report.
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