Journal
AGING AND DISEASE
Volume 10, Issue 4, Pages 818-833Publisher
INT SOC AGING & DISEASE
DOI: 10.14336/AD.2018.0802
Keywords
Mesenchymal stem cells; Bone regeneration; Small molecule; Resveratrol; MSC therapy
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Funding
- Mid-career Researcher Program [NRF-2018R1A2B6007376]
- Bio & Medical Technology Development Program of the National Research Foundation (NRF) - Ministry of Science, ICT & Future Planning [NRF-2017M3A9E8029722]
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Mesenchymal stem cells (MSCs) are an attractive cell source for regenerative medicine. However, MSCs age rapidly during long-term ex vivo culture 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, in vivo studies 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.
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