Long-term self-renewal of postnatal muscle-derived stem cells
Long-term self-renewal of postnatal muscle-derived stem cells
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DOI：
10.1091/mbc.e05-02-0169
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发表时间：
2005-07-01
影响因子：
3.3
通讯作者：
Huard, J
中科院分区：
文献类型：
--
作者：
Deasy, BM;Gharaibeh, BM;Huard, J
自我更新的能力是干细胞的一个决定性特征。自我补充活动维持组织稳态和再生。此外，干细胞治疗策略需要加深对自我更新过程基础的了解，以使研究人员和临床医生能够获得足够数量的未分化干细胞用于细胞和基因治疗。在这里，我们使用出生后肌肉来源的干细胞来测试无限干细胞复制的基本生物学假设。肌肉源性干细胞 (MDSC) 扩增 300 次群体倍增 (PD) 后没有显示出复制性衰老的迹象。 MDSC 在 200 个 PD 中保留其表型 (ScaI+/CD34+/desmin(低))，并且能够连续移植到 mdx 小鼠的骨骼肌中，该小鼠模拟杜氏肌营养不良。扩增至此水平的 MDSC 表现出与最小扩增细胞所表现出的高骨骼肌再生能力相当。扩增超过 200 个 PD 会导致肌肉再生能力降低、CD34 表达丧失、生肌活性丧失以及在软琼脂上生长增加，这表明由于 MDSC 的扩增和可能的转化而导致不可避免的细胞老化。尽管这些结果提出了细胞转化是否源自细胞培养或提供癌症干细胞证据的问题，但它们确立了出生后 MDSC 卓越的长期自我更新和再生能力。
The ability to undergo self-renewal is a defining characteristic of stem cells. Self-replenishing activity sustains tissue homeostasis and regeneration. In addition, stem cell therapy strategies require a heightened understanding of the basis of the self-renewal process to enable researchers and clinicians to obtain sufficient numbers of undifferentiated stem cells for cell and gene therapy. Here, we used postnatal muscle-derived stem cells to test the basic biological assumption of unlimited stem cell replication. Muscle-derived stem cells (MDSCs) expanded for 300 population doublings (PDs) showed no indication of replicative senescence. MDSCs preserved their phenotype (ScaI+/CD34+/desmin(low)) for 200 PDs and were capable of serial transplantation into the skeletal muscle of mdx mice, which model Duchenne muscular dystrophy. MDSCs expanded to this level exhibited high skeletal muscle regeneration comparable with that exhibited by minimally expanded cells. Expansion beyond 200 PDs resulted in lower muscle regeneration, loss of CD34 expression, loss of myogenic activity, and increased growth on soft agar, suggestive of inevitable cell aging attributable to expansion and possible transformation of the MDSCs. Although these results raise questions as to whether cellular transformations derive from cell culturing or provide evidence of cancer stem cells, they establish the remarkable long-term self-renewal and regeneration capacity of postnatal MDSCs.