Sertoli cells promote proliferation of bone marrow-derived mesenchymal stem cells in co-culture.

Bone marrow-derived mesenchymal stem cells (BMSCs) are a major source for cell transplantation. The proliferative ability of BMSCs is an important determinant of the efficiency of transplant therapy. Sertoli cells are ‘‘nurse’’ cells for development of sperm cells. Our recent study showed that Sertoli cells promoted proliferation of human umbilical cord mesenchymal stem cells (hUCMSCs) in co-culture. Studies by other groups also showed that Sertoli cells promoted growth of endothelial cells and neural stem cells. In this study, we investigated the effect of Sertoli cells on proliferation of BMSCs. Our results showed that Sertoli cells in co-culture significantly enhanced proliferation of BMSCs (P <0.01). Moreover, co-culture with Sertoli cells also markedly increased mRNA and/or protein expressions of Mdm2, p-Akt and Cyclin D1, and decreased p53 expression in BMSCs (P <0.01 or <0.05). These findings indicate that Sertoli cells have the potential to enhance proliferation of BMSCs.

Small concentrations of TGF-β1 promote proliferation of bone marrow-derived mesenchymal stem cells via activation of Wnt/β-catenin pathway.

Bone marrow-derived mesenchymal stem cells (BMSCs) are the most promising seed cells for cell transplant. The proliferation of BMSCs is one of the most important determinants of the efficiency of MSC-based transplant therapy. It has been reported that transforming growth factor-β1 (TGF-β1) activates Wnt/β-catenin signaling and regulates cell proliferation. In this study, we investigated the effect of low concentrations of TGF-β1 on proliferation of BMSCs and the related mechanisms. BMSCs were treated with 0, 1, 5 and 10 ng/L recombinant mouse TGF-β1 for 12 h. Cell proliferation was measured by cell counting and MTT assay, and the proliferation-related signals p53, Mdm2, Akt1, Wnt3, phospho-Akt and β-catenin were measured by quantitative polymerase chain reaction (qPCR) and/or Western blot. Our results showed that TGF-β1 at low concentrations induced BMSC proliferation and expression of Mdm2, Akt1, phospho-Akt, Wnt3 and β-catenin, and inhibited p53 expression in dose dependent manner. Importantly, β-catenin siRNA significantly inhibited TGF-β1-induced BMSC proliferation. These findings suggest that low concentrations of TGF-β1 can stimulate proliferation of BMSCs, which is at least partially dependent on the activation of Wnt/β-catenin pathway.