Different Facets of Aging in Human Mesenchymal Stem Cells
Different Facets of Aging in Human Mesenchymal Stem Cells
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DOI：
10.1089/ten.teb.2009.0825
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发表时间：
2010-08-01
影响因子：
6.4
通讯作者：
Zenke, Martin
中科院分区：
文献类型：
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作者：
Wagner, Wolfgang;Ho, Anthony D.;Zenke, Martin
间充质干细胞（MSC）必须培养扩增以获得用于治疗应用的相关细胞数量。然而，在2-3个月内，MSC的增殖速率衰减，直到它们最终达到衰老状态。这伴随着形态增大、表面标志物表达减少和分化潜力降低。目前尚不清楚长期培养对MSC制备的影响，可能涉及5个过程：（1）MSC由不同的亚群组成，在体外扩增过程中由于增殖速率不同，异质性发生变化;（2）培养中的细胞获得突变和其他随机的细胞缺陷;（3）在培养条件下，MSC的自我更新可能受损，导致逐渐分化;（4）细胞分裂的数量可能受到限制（e.例如，在一个实施例中，（5）复制性衰老可能与生物体的衰老过程有关。越来越多的人认识到，必须考虑长期培养，特别是在临床应用中。另一方面，复制性衰老的状态很难由群体倍增的数量或甚至由传代的数量来定义。细胞衰老的可靠分子测量是迫切需要的。
Mesenchymal stem cells (MSCs) have to be culture expanded to gain relevant cell numbers for therapeutic applications. However, within 2-3 months the proliferation rate of MSCs decays until they ultimately reach a senescent state. This is accompanied by enlarged morphology, reduced expression of surface markers, and decreased differentiation potential. So far it is only scarcely understood how long-term culture affects MSC preparations, and five processes seem to be involved: (1) MSCs are composed of different sub-populations, and due to different proliferation rates the heterogeneity changes in the course of in vitro expansion; (2) cells in culture acquire mutations and other stochastic cellular defects; (3) self-renewal of MSCs may be impaired under culture conditions, leading to gradual differentiation; (4) the number of cell divisions might be restricted (e. g., by loss of telomeres), and (5) replicative senescence might be associated with the aging process of the organism. There is a growing perception that long-term culture has to be taken into account-especially for clinical applications. On the other hand, the state of replicative senescence is poorly defined by the number of population doublings or even by the number of passages. Reliable molecular measures for cellular aging are urgently needed.