Regenerative Medicine Based on Muscle-Derived Stem Cells

The management and treatment of orthopaedic injuries has improved greatly over the last two decades, with the advent of minimally invasive operative techniques and sophisticated rehabilitation augmented by the always increasing knowledge of tissue biology and biomechanics. Despite the progress, scientists and orthopaedic surgeons continue to struggle with the limited healing capacity of damaged structures, such as degenerated articular cartilage, injured skeletal muscle, atrophic fracture nonunion, inflammatory conditions, and aging tissues. Therapeutic approaches that address the underlying pathophysiology of these disorders at the cellular and molecular level are quickly becoming a clinically applicable reality. Rapidly evolving field of stem cell therapy and gene therapy became integral part of regenerative medicine. Researchers have isolated and thoroughly characterized a population of skeletal muscle-derived stem cells (MDSCs) that display improved regenerative capacity in various tissues of the musculoskeletal system, when compared with skeletal myoblasts. These cells can be used to regenerate bone and articular cartilage, skeletal and cardiac muscle; they can repopulate bone marrow and repair peripheral nerve structures. Although the true origin of MDSCs remains unclear, their high degree of similarity with blood vessel–derived stem cells suggests their potential origin could be from the vascular wall. Here, we review the current knowledge concerning the use of gene therapy and tissue engineering applications based on MDSCs to improve the healing of various tissues of the musculoskeletal system, including bone and articular cartilage, as well as injured and diseased skeletal muscle.