Human mesenchymal stromal cells senesce with exogenous OCT4.

Abstract

The identification of mesenchymal stromal cells (MSC) from bone marrow by Friedenstein et al. dates back to 1970, but many questions remain unanswered about the biology of these cells. MSC have a wide clinical application because of their differentiation capacity and immunosuppressive properties. They are capable of self-renewal; however, the mechanism is poorly understood. The embryonic transcription factor Octamer binding transcription factor 4 (Oct4) has been suggested as an indicator of multipotency for mouse MSC. OCT4 has also been studied extensively for its involvement in self-renewal of embryonic stem cells and in cancer cells. Using a lentiviral-inducible vector, we modulated OCT4 expression in human MSC and studied its effect on the biology of these cells. Surprisingly, we found that the overexpression of OCT4 induced early senescence, as evidenced by increased expression of P14 and P16(INK4A) in MSC. These results indicate a differential role for exogenously expressed human OCT4 in adult and embryonic systems.