Age-Related Decreases of Serum-Response Factor Levels in Human Mesenchymal Stem Cells Are Involved in Skeletal Muscle Differentiation and Engraftment Capacity

Skeletal muscle (SkM) comprise ∼40% of human body weight. Injury or damage to this important tissue can result in physical disability, and in severe cases is difficult for its endogenous stem cell—the satellite cell—to reverse effectively. Mesenchymal stem cells (MSC) are postnatal progenitor/stem cells that possess multilineage mesodermal differentiation capacity, including toward SkM. Adult bone marrow (BM) is the best-studied source of MSCs; however, aging also decreases BMMSC numbers and can adversely affect differentiation capacity. Therefore, we asked whether human sources of developmentally early stage mesenchymal stem cells (hDE-MSCs) isolated from embryonic stem cells, fetal bone, and term placenta could be cellular sources for SkM repair. Under standard muscle-inducing conditions, hDE-MPCs differentiate toward a SkM lineage rather than cardiomyocytic or smooth muscle lineages, as evidenced by increased expression of SkM-associated markers and in vitro myotube formation. In vivo transplantation r...