6-Bromoindirubin-3′-oxime (BIO) induces proliferation of human mesenchymal stem cells (hMSCs)

The process of bone healing is a highly orchestrated process involving mesenchymal progenitor cells (e.g., periosteal stem cells). The cascade begins with recruitment and robust proliferation of these cells followed by differentiation to osteogenic and chondrogenic cell types, which produce matrix that eventually becomes mineralized. Thus, promoting proliferation of mesenchymal progenitors is a key step in recapitulating the healing process in a variety of bone defects (allografts, critical-sized defects, etc.). In this work, the small molecule GSK3β inhibitor 6-bromoindirubin-3´-oxime (BIO) was used to induce hMSC proliferation in vitro. In addition to a ~4 fold population increase, gene expression also indicated an increased state of hMSC “stemness” based upon elevated Sox2 and Nanog expression.