Mesenchymal Stem Cells as Regulators of Bone, Muscle, and Fat Formation

Abstract

The controversial concept of a “mesenchymal stem cell”, also known as “multipotent stromal cell” or “MSC”, has served as a cell biological foundation upon which to build and test hypotheses examining the complex relationships between bone, fat and skeletal muscle. Multiple independent studies have demonstrated the presence of MSC-like cells within connective tissues including bone, fascia, fat, marrow, skeletal muscle, and tendon. The MSC has been defined based on its plastic adherence and proliferative properties in vitro, its trilineage (adipogenic, chondrogenic, and osteogenic) differentiation ability, and its distinctive surface immunophenotype. Moreover, the differentiated MSC adipocytes, myocytes and osteoblasts secrete distinct profiles of growth factors termed “adipokines”, “myokines” and “osteokines”. These "-kines”, which include both anti- and pro-inflammatory cytokines, account in part for the MSC’s immunomodulatory and immunosuppressive functions in vitro and in vivo. Recent studies have focused on the MSC’s secretion of microvesicular “exosomes” containing cytokines, adhesive surface proteins, and microRNAs capable of positively or negatively modulating lineage specific signal transduction pathways. This chapter reviews the history and recent discoveries relating MSCs to the biological aging-associated pathologies of obesity, osteoporosis, and sarcopenia.