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.

间充质干细胞 (MSCs) 是治疗骨质疏松症的成骨细胞的潜在来源，但如何在体外培养条件下更好地保持 MSCs 的干性是 MSC 移植的主要挑战。已描述并广泛使用成纤维细胞生长因子 2 (FGF2) 补充剂来增加 MSCs 的扩增。累积证据表明，骨形态发生蛋白 2（BMP2；TGF-β 超家族的成员）是一种促进骨形成的分泌蛋白，可以调节细胞生长、分化和发育。在这里我们发现 BMP2 与 FGF2 结合，不仅增强了 Macaca 骨髓来源的 MSCs 的增殖，而且在体外短期扩张后增强了它们的成骨潜力。在长期扩张过程中，这些细胞仍然保留了它们的成骨潜力以及多能 MSC 的其他功能特征，这些特征在缺乏 BMP2 的情况下逐渐丧失。此外，BMP 拮抗剂 Noggin 不影响 MSC 扩增和成骨潜力。本研究表明调节BMP信号可以维持MSCs在扩张过程中的有效性，促进MSCs在骨修复中的临床应用。