Choi Yoorim, Yoon Dong Suk, Lee Kyoung-Mi, Choi Seong Mi, Lee Myon-Hee, Park Kwang Hwan, Han Seung Hwan, Lee Jin Woo
1Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul 03722, South Korea.
2Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, South Korea.
Aging Dis. 2019 Aug 1;10(4):818-833. doi: 10.14336/AD.2018.0802. eCollection 2019 Aug.
Mesenchymal stem cells (MSCs) are an attractive cell source for regenerative medicine. However, MSCs age rapidly during long-term 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 cultivation. Resveratrol (RSV) has been highlighted as a therapeutic candidate for bone disease. Although RSV treatment has beneficial effects on bone-forming cells, 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.
间充质干细胞（MSCs）是再生医学中一种具有吸引力的细胞来源。然而，MSCs在长期培养过程中会迅速老化，并在达到细胞治疗的有效细胞剂量（ECD）之前丧失其治疗潜力。因此，有效的MSC治疗的一个先决条件是开发在长期培养过程中保留治疗潜力的细胞培养方法。白藜芦醇（RSV）已被视为治疗骨疾病的候选药物。尽管RSV治疗对成骨细胞有有益作用，但相关研究仍很缺乏。当前研究表明，经RSV诱导长期（从原代培养日期起6周）培养的MSCs尽管达到了ECD，但仍保留其增殖和分化潜力。RSV作用的机制完全取决于MSC培养中的SIRT1-SOX2轴。在大鼠颅骨缺损模型中，RSV诱导显著改善了MSC移植后的骨再生。本研究通过提供一种使用植物多酚RSV的新策略，展示了一种有效治疗骨缺损的MSC治疗实例。
