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间充质干细胞与微小RNA疗法治疗肌肉骨骼疾病

Mesenchymal Stem Cell and MicroRNA Therapy of Musculoskeletal Diseases.

作者信息

Chung Myung-Jin, Son Ji-Yoon, Park SunYoung, Park Soon-Seok, Hur Keun, Lee Sang-Han, Lee Eun-Joo, Park Jin-Kyu, Hong Il-Hwa, Kim Tae-Hwan, Jeong Kyu-Shik

机构信息

Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea.

Stem Cell Therapeutic Research Institute, Kyungpook National University, Daegu, Korea.

出版信息

Int J Stem Cells. 2021 May 30;14(2):150-167. doi: 10.15283/ijsc20167.

Abstract

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 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.

摘要

间充质干细胞(MSCs)在肌肉骨骼疾病(MSDs)中的治疗效果已在许多人体和动物研究中得到验证。尽管一些组织中含有间充质干细胞,但从这些组织中收获的细胞数量和增殖速率不足以进行持续移植。为了产生并维持稳定的间充质干细胞,人们进行了许多尝试,试图将多能干细胞(iPSCs)诱导分化为间充质干细胞。特别值得一提的是,干细胞分泌因子的旁分泌作用能够促进受损组织中靶细胞的再生和分化。微小RNA(miRNAs)作为分泌因子之一,是一类调控基因翻译的小型非编码RNA。众所周知,微小RNA通过外泌体帮助干细胞与其周围的生态位进行通讯,从而调节干细胞的增殖和分化。尽管目前针对肌肉骨骼疾病的治疗性微小RNA的研究正在进行,但对间充质干细胞分泌的特定微小RNA的研究仍然很少。因此,我们的最终目标是从诱导多能干细胞来源的间充质干细胞中获得足够数量的外泌体,并将其开发成治疗药物,进一步筛选特定的微小RNA,并提供安全的无细胞临床环境,以无细胞状态将它们递送至靶细胞。这篇综述文章重点关注肌肉骨骼疾病的干细胞治疗、调控肌肉骨骼疾病的特定微小RNA以及新方法的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0931/8138662/18f9e561e8b2/ijsc-14-2-150-f1.jpg

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