Mesenchymal stem cells (MSCs) are an attractive cell source for regenerative medicine. However, MSCs age rapidly during long-term ex vivoculture and lose their therapeutic potential before they reach effective cell doses (ECD) for cell therapy. Thus, a prerequisite for effective MSC therapy is the development of cell culture methods to preserve the therapeutic potential during long-term ex vivo cultivation. Resveratrol (RSV) has been highlighted as a therapeutic candidate for bone disease. Although RSV treatment has beneficial effects on bone-forming cells,invivostudies are lacking.The current study showed that long-term (6 weeks from primary culture date)-cultured MSCs with RSV induction retained their proliferative and differentiation potential despite reaching ECD. The mechanism of RSV action depends entirely on the SIRT1-SOX2 axis in MSC culture. In a rat calvarial defect model, RSV induction significantly improved bone regeneration after MSC transplantation. This study demonstrated an example of efficient MSC therapy for treating bone defects by providing a new strategy using the plant polyphenol RSV.
Bibliographical noteFunding Information:
This work was supported by the Mid-career Researcher Program (NRF-2018R1A2B6007376) and the Bio & Medical Technology Development Program (NRF-2017M3A9E8029722) of the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning.
All Science Journal Classification (ASJC) codes
- Pathology and Forensic Medicine
- Geriatrics and Gerontology
- Clinical Neurology
- Cell Biology