Department of Physiology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
Laboratory of Immunology and Experimental Transplantation, São José do Rio Preto Medical School, São José do Rio Preto, São Paulo, Brazil.
Stem Cell Rev Rep. 2019 Aug;15(4):463-473. doi: 10.1007/s12015-019-09897-0.
Mesenchymal stem cells (MSCs), also known as multipotent mesenchymal stromal stem cells, are found in the perivascular space of several tissues. These cells have been subject of intense research in the last decade due to their low teratogenicity, as well as their ability to differentiate into mature cells and to secrete immunomodulatory and trophic factors. However, they usually promote only a modest benefit when transplanted in experimental disease models, one of the limitations for their clinical application. The CRISPR-Cas system, in turn, is highlighted as a simple and effective tool for genetic engineering. This system was tested in clinical trials over a relatively short period of time after establishing its applicability to the edition of the mammalian cell genome. Similar to the research evolution in MSCs, the CRISPR-Cas system demonstrated inconsistencies that limited its clinical application. In this review, we outline the evolution of MSC research and its applicability, and the progress of the CRISPR-Cas system from its discovery to the most recent clinical trials. We also propose perspectives on how the CRISPR-Cas system may improve the therapeutic potential of MSCs, making it more beneficial and long lasting.
间充质干细胞(MSCs),也称为多能间充质基质干细胞,存在于几种组织的血管周围空间中。由于其致畸性低,以及分化为成熟细胞和分泌免疫调节和营养因子的能力,这些细胞在过去十年中成为研究热点。然而,当它们被移植到实验性疾病模型中时,通常只能带来适度的益处,这是它们临床应用的一个限制。CRISPR-Cas 系统则被突出为一种简单有效的基因工程工具。在建立其对哺乳动物细胞基因组编辑的适用性后,该系统在相对较短的时间内就在临床试验中得到了测试。与 MSCs 的研究演变类似,CRISPR-Cas 系统也表现出不一致性,限制了其临床应用。在这篇综述中,我们概述了 MSC 研究及其适用性的演变,以及 CRISPR-Cas 系统从发现到最近临床试验的进展。我们还提出了一些观点,即 CRISPR-Cas 系统如何提高 MSCs 的治疗潜力,使其更有益和更持久。