Different Effects of Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor-2 on Myogenic Differentiation of Human Mesenchymal Stem Cells

Figure 9

PMSC differentiation into skeletal muscle using the insulin-like growth factor system. PMSCs isolated from the chorionic villus of preterm human placenta expressed high levels of pluripotency-associated markers under normal growth conditions (10% FBS). As these cells differentiated into skeletal muscle, the levels of these markers decreased, and the cells committed to the muscle lineage, indicated by Pax3/7 expression. Once committed to differentiation, PMSCs subsequently decreased Pax3/7 expression and increased muscle differentiation markers (MyoG, MyoD, and MHC) as myoblasts aligned and fuse to form multinucleated myofibers. IGF-1 and IGF-2 binds to the IGF-1R and activates its intrinsic tyrosine kinase activity resulting in signaling that accelerated muscle differentiation via downstream signals including PI3K-AKT-mTOR and the RAF-MEK-ERK (MAPK) pathway. Due to IGFBP-6 intracellular and extracellular locations, IGFBP-6 demonstrated both IGF-dependent and IGF-independent effects on PMSC muscle differentiation. Extracellular IGFBP-6 binds IGFs and enhances the muscle differentiation process through the IGF-1R, while intracellular IGFBP-6 directly impacted PMSC muscle differentiation through an unknown mechanism.