Muscle reconstitution by muscle satellite cell descendants with stem cell-like properties
Muscle reconstitution by muscle satellite cell descendants with stem cell-like properties
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DOI：
10.1242/dev.01395
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发表时间：
2004-11-01
期刊：
影响因子：
4.6
通讯作者：
Inagawa-Ogashiwa, M
中科院分区：
文献类型：
--
作者：
Hashimoto, N;Murase, T;Inagawa-Ogashiwa, M
最近的研究表明，成肌细胞培养中具有干细胞样特征的独特亚群负责肌内移植后新肌纤维的形成。干细胞样细胞的鉴定和分离将对人类肌肉疾病的成肌细胞转移治疗具有重要意义。使用小鼠肌肉卫星细胞的克隆培养系统，我们已经确定了两种细胞类型，指定的'圆细胞'和'厚细胞'，在克隆来自单个肌肉卫星细胞，已采取从慢肌或快肌。卫星细胞的克隆分析表明，圆形细胞是静止的卫星细胞在成年肌肉的直接后代。在单肌纤维培养中，圆形细胞首先形成集落，然后产生后代，厚细胞，在适当的培养条件下进行肌原性和成骨终末分化。厚细胞，而不是圆细胞，响应终端分化诱导信号。圆形细胞高水平表达卫星细胞的特异性标志物Pax7。成肌细胞移植实验表明，圆形细胞比厚细胞更有效地重建肌纤维。此外，圆形细胞恢复mdx裸鼠肌纤维中的肌营养不良蛋白，即使只有5000个细胞被转移到腓肠肌。这些结果表明，圆形细胞是具有干细胞样特征的卫星细胞后代，并且代表了用于改善肌肉再生的供体细胞的有用来源。
Recent studies have demonstrated that a distinct subpopulation with stem cell-like characteristics in myoblast culture is responsible for new muscle fiber formation after intramuscular transplantation. The identification and isolation of stem-like cells would have significant implications for successful myogenic cell transfer therapy in human muscle disorders. Using a clonal culture system for mouse muscle satellite cells, we have identified two cell types, designated 'round cells' and I thick cells', in clones derived from single muscle satellite cells that have been taken from either slow or fast muscle. Clonal analysis of satellite cells revealed that the round cells are immediate descendants of quiescent satellite cells in adult muscle. In single-myofiber culture, round cells first formed colonies and then generated progeny, thick cells, that underwent both myogenic and osteogenic terminal differentiation under the appropriate culture conditions. Thick cells, but not round cells, responded to terminal differentiation-inducing signals. Round cells express Pax7, a specific marker of satellite cells, at high levels. Myogenic cell transfer experiments showed that round cells reconstitute myofibers more efficiently than thick cells. Furthermore, round cells restored dystrophin in myofibers of mdx nude mice, even when as few as 5000 cells were transferred into the gastrocnemius muscle. These results suggest that round cells are satellite-cell descendants with stem cell-like characteristics and represent a useful source of donor cells to improve muscle regeneration.