α7 integrin expressing human fetal myogenic progenitors have stem cell-like properties and are capable of osteogenic differentiation

α7 integrin expressing human fetal myogenic progenitors have stem cell-like properties and are capable of osteogenic differentiation
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DOI:
10.1016/j.yexcr.2006.09.017
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发表时间:
2006-12-10
影响因子:
3.7
通讯作者:
Kramer, Randall H.
Kramer, Randall H.
中科院分区:
医学3区
文献类型:
--
作者:
Ozeki, Nobuaki;Lim, Moon;Kramer, Randall H.

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在肌肉发育过程中,前体细胞融合形成肌纤维。成年肌肉损伤后,静止的卫星细胞被激活,以类似于胎儿发育的方式再生肌肉。最近的研究表明,小鼠骨骼肌成肌细胞可以沿沿着多个细胞谱系分化,包括成骨细胞途径。然而,很少有人知道人类肌原细胞的多能性。在这里,我们分离肌源性前体细胞从人胎儿和成人肌肉层粘连蛋白结合α 7整合素的排序,并证明其分化潜力和改变的粘附行为。α 7阳性人胎儿祖细胞在形成肌管方面是有效的,并且大多数表达已知的肌肉标记物,包括M-钙粘蛋白和c-Met,但是结蛋白和MyoD表达是异质的。为了测试它们的多能分化潜能,对α阳性胎儿细胞的富集群体进行诱导方案。虽然成肌细胞似乎致力于肌肉谱系,但在BMP-2存在下,它们可以沿着成骨细胞途径沿着分化。有趣的是,成骨细胞表现出改变的粘附和迁移活性,反映了生长因子诱导的整合素表达的变化。这些结果表明,表达α 7的胎儿成肌细胞能够分化成成骨细胞谱系与整合素谱的协调开关,并可能代表一种机制,促进归巢和肌源性干细胞的组织修复和重塑的招聘。(c)2006年爱思唯尔公司All rights reserved.
During muscle development, precursor cells fuse to form myofibers. Following injury in adult muscle, quiescent satellite cells become activated to regenerate muscle in a fashion similar to fetal development. Recent studies indicate that murine skeletal myoblasts can differentiate along multiple cell lineages including the osteoblastic pathway. However, little is known about the multipotency of human myogenic cells. Here, we isolate myogenic precursor cells from human fetal and adult muscle by sorting for the laminin-binding alpha 7 integrin and demonstrate their differentiation potential and alteration in adhesive behavior. The alpha 7-positive human fetal progenitors were efficient at forming myotubes and a majority expressed known muscle markers including M-cadherin and c-Met, but were heterogeneous for desmin and MyoD expression. To test their pluripotent differentiation potential, enriched populations of alpha-positive fetal cells were subjected to inductive protocols. Although the myoblasts appeared committed to a muscle lineage, they could be converted to differentiate along the osteoblastic pathway in the presence of BMP-2. Interestingly, osteogenic cells showed altered adhesion and migratory activity that reflected growth factor-induced changes in integrin expression. These results indicate that alpha 7-expressing fetal myoblasts are capable of differentiation to osteoblast lineage with a coordinated switch in integrin profiles and may represent a mechanism that promotes homing and recruitment of myogenic stem cells for tissue repair and remodeling. (c) 2006 Elsevier Inc. All rights reserved.