Tranylcypromine Attenuates Senescence in Dental Pulp Stem Cells

Background: Mesenchymal stem cells (MSCs) are spindle shaped and multipotent stromal cells which can differentiate into a variety of cell types. Human dental pulp stem cells (hDPSCs) display self-renewal and multi-lineage differentiation potential as well as possess immunomodulatory properties and potential clinical applications. Objective: Preliminary study demonstrated that MSCs have advantage in regenerative and immune treatments. However, the senescence and spontaneous differentiation of MSCs during long term in vitro culturing restrict the amount and quantity of cells for scientific research and clinical application. Thus, it is crucial the develop methods maintain the mesenchymal properties of MSCs during long-term culture. Such data on the senescence of hDPSCs have not been reported. Method: Here, we investigated the differentiation potential, culture-related phenotypes and senescence of hDPSCs. hDPSCs showed senescence properties after serially passaged implied by changed cell morphology, decreasing proliferation ability, increasing of SA-β-Gal positive cells, low levels of pluripotent and proliferative genes expression, and high levels of genes expression which related to senescence. We also investigated the effects of tranylpromine (TCP), a monoamine oxidase inhibitor to against DPSCs senescence. Results and Conclusion: Results demonstrated that low concentration of TCP not only significantly improved the proliferation ability and delayed the senescence of hDPSCs, but also increased the expression of pluripotent and proliferative genes, such as octamer-binding transcription factor 4 (OCT4), Nanog, (sex-determining region Y)-box (SOX2), telomerase reverse-transcriptase (TERT) and C-X-C chemokine receptor 4 (CXCR4). Whats more, low concentration of TCP can suppress the spontaneous differentiation of hDPSCs and the expression of senescence marker p53. Altogether, our study showed the characteristics of hDPSCs after long term culture in vitro and may provide an efficient approach to delay or even reverse the senescence of hDPSCs.