Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion
Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion
复制标题
DOI：
10.1634/stemcells.22-5-675
复制
发表时间：
2004-01-01
期刊：
影响因子：
5.2
通讯作者：
Bellantuono, I
中科院分区：
文献类型：
--
作者：
Baxter, MA;Wynn, RF;Bellantuono, I
人骨髓基质细胞（marrow stromal cells，MSCs）可从骨髓中分离，并在体内外分化为多种组织。这些特性使它们成为细胞和基因治疗的有前途的工具。由于缺乏特异性MSC标记物和骨髓中MSC的低频率，在临床使用之前需要通过体外扩增分离它们。这可能会严重降低MSC的增殖能力，以至于残余的增殖潜力不足以在回输后维持长期的组织再生。在这项研究中，我们通过将体外扩增过程中的端粒丢失率与其体内行为相关联来确定体外扩增对MSC复制能力的影响。我们报告说，即使是涉及最低限度的扩展协议诱导骨髓间充质干细胞的快速老化，损失相当于约一半的总复制寿命。
Human marrow stromal cells (MSCs) can be isolated from bone marrow and differentiate into multiple tissues in vitro and in vivo. These properties make them promising tools in cell and gene therapy. The lack of a specific MSC marker and the low frequency of MSCs in bone marrow necessitate their isolation by in vitro expansion prior to clinical use. This may severely reduce MSC proliferative capacity to the point that the residual proliferative potential is insufficient to maintain long-term tissue regeneration upon reinfusion. In this study we determined the effect of in vitro expansion on the replicative capacity of MSCs by correlating their rate of telomere loss during in vitro expansion with their behavior in vivo. We report that even protocols that involve minimal expansion induce a rapid aging of MSCs, with losses equivalent to about half their total replicative lifespan.