Chapter 62 - Musculoskeletal Tissue Injury and Repair: Role of Stem Cells, Their Differentiation, and Paracrine Effects

Abstract

Muscle injury represents a challenging problem in traumatology and sports medicine. Injured skeletal muscle can repair itself via the activation of muscle progenitor cells, including stem cells, which promote muscle regeneration; however, the deposition of collagen in the injured area leads to the formation of fibrosis and results in the incomplete functional recovery of the muscle and a propensity for injury recurrence. This review will summarize the current knowledge of skeletal muscle injury and repair and highlight approaches that improve muscle healing via the prevention of fibrosis and increase in muscle regeneration through the use of muscle-derived stem cells. With the explosion of stem cell studies during the 1990s, the field of stem cell therapeutics has been centered on the defining stem cell characteristics of self-renewal and multilineage differentiation. New insights in recent years suggest that stem cells may do much more than simply differentiate, in fact, even when differentiation does not occur the transplantation of stem cells still leads to efficient tissue repair. The therapeutic benefits may be due to the less well investigated, yet unique characteristics of robust stem cells – cell survival and subsequent paracrine signaling of the host cells. The stem cells’ intrinsic ability to survive cell transplantation may be directly related to the bioactive factors that they secrete to promote the healing of host tissue. The trophic activity of stem cells inhibits tissue damage (including fibrosis formation and cell death) at the site of injury, stimulates proliferation of host cells that contribute to tissue repair, modulates inflammatory and immune rejection responses and stimulates angiogenesis, in some cases. This chapter discusses the role of cell survival and paracrine signaling in stem cell-mediated repair using examples from skeletal and cardiac muscle and also includes examples of bone and cartilage repair in order to illustrate that this stem cell behavior extends to the repair and regeneration of other tissues.