The therapeutic effects of mesenchymal stem cells (MSCs) in musculoskeletal diseases (MSDs) have been verified in many human and animal studies. Although some tissues contain MSCs, the number of cells harvested from those tissues and rate of proliferation in vitro are not enough for continuous transplantation. In order to produce and maintain stable MSCs, many attempts are made to induce differentiation from pluripotent stem cells (iPSCs) into MSCs. In particular, it is also known that the paracrine action of stem cell-secreted factors could promote the regeneration and differentiation of target cells in damaged tissue. MicroRNAs (miRNAs), one of the secreted factors, are small non-coding RNAs that regulate the translation of a gene. It is known that miRNAs help communication between stem cells and their surrounding niches through exosomes to regulate the proliferation and differentiation of stem cells. While studies have so far been underway targeting therapeutic miRNAs of MSDs, studies on specific miRNAs secreted from MSCs are still minimal. Hence, our ultimate goal is to obtain sufficient amounts of exosomes from iPSC-MSCs and develop them into therapeutic agents, furthermore to select specific miRNAs and provide safe cell-free clinical setting as a cell-free status with purpose of delivering them to target cells. This review article focuses on stem cell therapy on MSDs, specific microRNAs regulating MSDs and updates on novel approaches.

中文翻译：

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肌肉骨骼疾病的间充质干细胞和 MicroRNA 疗法。

间充质干细胞 (MSC) 在肌肉骨骼疾病 (MSD) 中的治疗作用已在许多人类和动物研究中得到证实。虽然一些组织含有 MSC，但从这些组织中收获的细胞数量和体外增殖率不足以连续移植。为了产生和维持稳定的 MSC，进行了许多尝试以诱导从多能干细胞 (iPSC) 向 MSC 的分化。尤其是干细胞分泌因子的旁分泌作用可以促进受损组织中靶细胞的再生和分化。MicroRNA (miRNA) 是分泌因子之一，是调节基因翻译的小型非编码 RNA。众所周知，miRNA通过外泌体帮助干细胞与其周围生态位之间的通讯，从而调节干细胞的增殖和分化。虽然迄今为止针对 MSD 的治疗性 miRNA 的研究一直在进行，但对 MSC 分泌的特定 miRNA 的研究仍然很少。因此，我们的最终目标是从 iPSC-MSC 中获得足够数量的外泌体并将其开发成治疗剂，此外还可以选择特定的 miRNA 并提供安全的无细胞临床环境作为无细胞状态，目的是将它们递送至靶细胞。这篇综述文章的重点是 MSD 的干细胞疗法、调节 MSD 的特定 microRNA 以及新方法的更新。