Cellular senescence and spontaneous differentiation are critical phenomena that impair long-term study of human mesenchymal stem cells (hMSCs) in vitro, despite its high proliferation rate and multipotency comparing to those of differentiated cells derived from different tissues. In addition, bone formation capacity, which might be the most critical factor in implantology and periodontal regeneration, would also be severely influenced by cellular senescence and spontaneous differentiation of hMSCs. The present study was designed to overcome these problems and also explored to drive hMSCs toward stemness and thus to enhance osteogenesis.