Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore; Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119288, Singapore.
Stem Cell Reports. 2021 Apr 13;16(4):694-707. doi: 10.1016/j.stemcr.2021.01.021. Epub 2021 Feb 25.
Human mesenchymal stem/stromal cell (hMSC)-based cell therapies are promising for treating a variety of diseases. The unique immunomodulatory properties of hMSCs have extended their therapeutic potential beyond tissue regeneration. However, extensive pre-clinical culture expansion inevitably drives cells toward replicative "aging" and a consequent decline in quality. These "in vitro-aged" hMSCs resemble biologically aged cells, which have been reported to show senescence signatures, diminished immunosuppressive capacity, and weakened regenerative potential as well as pro-inflammatory features. In this review, we have surveyed the literature to explore the intimate relationship between the inflammatory status of hMSCs and their in vitro aging process. We posit that a shift from an anti-inflammatory to a pro-inflammatory phenotype of culture-expanded hMSCs contributes to a deterioration in their therapeutic efficacy. Potential molecular and cellular mechanisms underpinning this phenomenon have been discussed. We have also highlighted studies that leverage these mechanisms to make culture-expanded hMSCs more amenable for clinical use.
基于人间质/基质干细胞（hMSC）的细胞疗法在治疗多种疾病方面具有广阔的应用前景。hMSC 的独特免疫调节特性扩展了其治疗潜能，超越了组织再生。然而，广泛的临床前培养扩增不可避免地导致细胞向复制性“衰老”以及随之而来的质量下降。这些“体外衰老”的 hMSC 类似于生物学上衰老的细胞，已有报道表明其具有衰老特征、免疫抑制能力降低、再生潜能减弱以及促炎特征。在这篇综述中，我们查阅了文献，以探讨 hMSC 的炎症状态与其体外衰老过程之间的密切关系。我们假设，培养扩增的 hMSC 从抗炎表型向促炎表型的转变，导致其治疗效果恶化。我们讨论了支持这一现象的潜在分子和细胞机制。我们还强调了利用这些机制使培养扩增的 hMSC 更适用于临床应用的研究。
