Bone morphogenetic protein signaling is involved in human mesenchymal stem cell survival in serum-free medium

Bone marrow human mesenchymal stem cells (hMSCs) are known to survive in serum-free media, when most normal somatic cells do not survive. We found that the endogenously-activated bone morphogenetic protein (BMP) pathway is involved in this cellular behavior. Under this culture condition, phosphorylated Smad1 (PSmad1), the transducer of this signal, is localized in the hMSC nuclei. In addition, inhibition of this pathway with noggin, a BMP antagonist, elicits a caspase-dependent hMSC's death in a concentration-dependent manner. Furthermore, exogenously added BMP4 alleviates the noggin effect, restoring cell survival, and suggesting that BMP signal is essential for hMSC survival under serum deprivation conditions. Altogether these findings demonstrate for the first time an endogenous survival pathway of hMSCs driven by a BMP signal. Such a survival mechanism might be involved in the maintenance of the hMSC population within their bone marrow niche.