Human Muscle-Derived Cell Populations Isolated by Differential Adhesion Rates: Phenotype and Contribution to Skeletal Muscle Regeneration in Mdx/SCID Mice

Human Muscle-Derived Cell Populations Isolated by Differential Adhesion Rates: Phenotype and Contribution to Skeletal Muscle Regeneration in Mdx/SCID Mice
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DOI:
10.1089/ten.tea.2010.0553
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发表时间:
2012-02-01
影响因子:
4.1
通讯作者:
Deasy, Bridget M.
Deasy, Bridget M.
中科院分区:
医学3区
文献类型:
--
作者:
Chirieleison, Steven M.;Feduska, Joseph M.;Deasy, Bridget M.

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在杜氏肌营养不良小鼠(mdx)中,通过预板方法从小鼠骨组织中分离出的肌肉来源干细胞(MDSCs)显示出了向肌源性谱系发展的能力,并且比骨骼肌和心肌中的成肌细胞更有效地再生。然而,到目前为止,这些研究还没有转化为人类肌肉细胞。在这里,我们描述了通过预板技术分离候选人类MDSCs,这些MDSCs表现出与小鼠相似的肌肉生成和再生特征。使用预板分离方法,我们比较了粘附速度较快的细胞,预板2 (PP2)和粘附速度较慢的细胞,预板6 (PP6)。人PP6细胞表达间充质干细胞的几种标记物,基于其表达CD146和肌生成标记物desmin和CD56,与人PP2(一种成肌细胞样群体)不同。在mdx/SCID小鼠腓肠肌移植后,我们观察到PP6细胞参与肌肉再生的水平明显高于PP2细胞移植。本研究支持了先前关于小鼠预板细胞的一些发现,也发现了小鼠和人类肌肉预板细胞之间的一些差异。
Muscle-derived stem cells (MDSCs) isolated from murine skeletal tissue by the preplate method have displayed the capability to commit to the myogenic lineage and regenerate more efficiently than myoblasts in skeletal and cardiac muscle in murine Duchenne Muscular Dystrophy mice (mdx). However, until now, these studies have not been translated to human muscle cells. Here, we describe the isolation, by a preplate technique, of candidate human MDSCs, which exhibit myogenic and regenerative characteristics similar to their murine counterparts. Using the preplate isolation method, we compared cells that adhere faster to the flasks, preplate 2 (PP2), and cells that adhere slower, preplate 6 (PP6). The human PP6 cells express several markers of mesenchymal stem cells and are distinct from human PP2 (a myoblast-like population) based on their expression of CD146 and myogenic markers desmin and CD56. After transplantation to the gastrocnemius muscle of mdx/SCID mice, we observe significantly higher levels of PP6 cells participating in muscle regeneration as compared with the transplantation of PP2 cells. This study supports some previous findings related to mouse preplate cells, and also identifies some differences between mouse and human muscle preplate cells.