Long-term expansion and enhanced osteogenic potential of Macaca MSCs via BMP signaling modulation

Mesenchymal stem cells (MSCs) are a potential source of osteoblasts for the treatment of osteoporosis, but how to better preserve the stemness of MSCs in vitro culture conditions is the main challenge for MSC transplantation. The use of fibroblast growth factor 2 (FGF2) supplement has been described and used extensively to increase the expansion of MSCs. Cumulative evidence indicates that bone morphogenetic protein 2 (BMP2; a member of the TGF-β superfamily) is a secreted protein that promotes bone formation, which can regulate cell growth, differentiation, and development. Here we found that BMP2, in combination with FGF2, not only enhanced the proliferation of Macaca bone marrow-derived MSCs but also strengthened their osteogenic potential after short-term expansion in vitro. During long-term expansion, these cells still retained their osteogenic potential as well as other functional characteristics of pluripotent MSCs, which are gradually lost in the absence of BMP2. In addition, the BMP antagonist Noggin did not affect MSC expansion and the osteogenic potential. This study demonstrates that the regulation of BMP signaling can maintain the effectiveness of MSCs during expansion, which promotes the clinical application of MSCs in bone repair.