3-D成球培养MSCs的研究进展及临床应用前景

Research progress and clinical prospect of three-dimensional spheroid culture of mesenchymal stem cells

目的总结近年来3-D成球培养MSCs的研究进展及临床应用前景。方法广泛查阅国内外3-D成球培养MSCs的相关研究,重点关注3-D培养模式下MSCs细胞球的形成机制,3-D培养的MSCs细胞球与传统贴壁培养的MSCs在生物功能上存在的差异,以及造成这些差异的生物学机制,探讨MSCs细胞球的临床应用前景。结果与传统贴壁培养的MSCs相比,3-D培养的MSCs细胞球在抗凋亡、多向分化、旁分泌、抗炎等多项生物功能上明显增强,其机制与细胞骨架的改变、细胞接触的增加和低氧微环境的刺激有关,在动物实验中对于难愈性创面的修复、缺血组织的修复、组织重塑具有显著治疗效果,有广阔临床应用前景。结论 3-D培养的MSCs细胞球较传统贴壁培养的MSCs具有更强的生物功能和治疗效果,可成为临床上优化干细胞疗法、提高其治疗效果的一种手段。

Objective To review the research progress and clinical prospect of three-dimensional spheroid culture of mesenchymal stem cells （MSCs）. Methods Recent literature about three-dimensional spheroid culture of MSCs was summarized, mainly on the formation of MSCs spheroids collected by three-dimensional culture, differences between MSCs spheroids and MSCs collected by traditional two-dimensional culture, and the mechanism underlying these differences. Last, its clinical prospect was discussed. Results Compared with MSCs collected by traditional two-dimensional culture, MSCs spheroids collected by three-dimensional culture get a salient up-regulation in anti-apoptosis, multiple differentiation potential, paracrine, and anti-inflammatory effect, which may be related to the morphology and cytoskeleton organization, cell-to-cell contact and gap junctions, and the hypoxia microenvironment. The animal experiments show obvious effects in repair of refractory wounds, repair of ischemic injury, and tissue remodeling, so MSCs spheroid has broad clinical prospect. Conclusion MSCs spheroids collected by three-dimensional culture have stronger biological potential and treatment effect than MSCs collected by traditional two-dimensional culture, MSCs spheroids can be used to optimize stem cell therapy and improve its treatment effect.