THE ROLE OF INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN-6 IN THE DIFFERENTIATION OF PLACENTAL MESENCHYMAL STEM CELLS INTO SKELETAL MUSCLE

Insulin-like growth factor binding protein-6 (IGFBP-6), a component of the stem cell niche involved in the differentiation of skeletal muscle myogenesis, is expressed in developing muscle cells and is the main regulator of IGF-II. In this study, I investigated the role of IGFBP-6 in the commitment of skeletal muscle derivation from placenta mesenchymal stem cells (PMSCs). I hypothesized that IGFBP-6 inhibits the temporal maintenance of PMSCs and promotes the differentiation of PMSCs into muscle via both extracellular and intracellular mechanisms. PMSCs can differentiate into muscle cells expressing the muscle markers Pax3/7, MyoD, and Myogenin with the formation of multi-nucleated fibers. Under differentiation conditions, silencing IGFBP-6 increased Pax3/7 and decreased OCT4 levels. In contrast, under non-differentiation conditions, there was a significant increase in Pax3/7 levels at day 7 with intracellular and extracellular increase of IGFBP-6, similarly silencing IGFBP-6 under non-differentiation conditions significantly increased Pax3/7 at 24 hours and decreased OCT4 levels over time same as in differentiation conditions. I concluded that increasing lGFBP-6 promotes PMSCs differentiation with more prominent effects at the beginning of the differentiation process, while silencing IGFBP-6 has more dramatic effects on PMSCs. Knowledge of the effects of IGFBP-6 on muscle differentiation will help improve strategies for skeletal muscle regeneration therapies using stem cells