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诱导性肌肉源干细胞样细胞的功能性神经元分化及其治疗意义。

Functional Neuronal Differentiation of Injury-Induced Muscle-Derived Stem Cell-Like Cells with Therapeutic Implications.

机构信息

Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM) at the University of Texas Health Science Center at Houston, TX, Houston, 77030, USA.

Department of Pediatric Surgery, University of Texas McGovern Medical School at Houston, Houston, 77030, TX, USA.

出版信息

Sci Rep. 2017 Apr 26;7(1):1177. doi: 10.1038/s41598-017-01311-4.

DOI:10.1038/s41598-017-01311-4
PMID:28446779
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5430871/
Abstract

Mammalian skeletal muscles contain a number of heterogeneous cell populations. Our previous study characterized a unique population of myogenic lineage stem cells that can be isolated from adult mammalian skeletal muscles upon injury. These injury-induced muscle-derived stem cell-like cells (iMuSCs) displayed a multipotent state with sensitiveness and strong migration abilities. Here, we report that these iMuSCs have the capability to form neurospheres that represent multiple neural phenotypes. The induced neuronal cells expressed various neuron-specific proteins, their mRNA expression during neuronal differentiation recapitulated embryonic neurogenesis, they generated action potentials, and they formed functional synapses in vitro. Furthermore, the transplantation of iMuSCs or their cell extracts into the muscles of mdx mice (i.e., a mouse model of Duchenne Muscular Dystrophy [DMD]) could restore the morphology of their previously damaged neuromuscular junctions (NMJs), suggesting that the beneficial effects of iMuSCs may not be restricted to cell restoration alone, but also due to their transient paracrine actions. The current study reveals the essential role of iMuSCs in the restoration of NMJs related to injuries and diseases.

摘要

哺乳动物的骨骼肌包含许多异质的细胞群体。我们之前的研究描述了一种独特的成肌谱系干细胞群体，它可以在受伤后从成年哺乳动物的骨骼肌中分离出来。这些损伤诱导的肌肉源性干细胞样细胞（iMuSCs）表现出多能状态，具有敏感性和强大的迁移能力。在这里，我们报告说这些 iMuSCs 有形成神经球的能力，代表多种神经表型。诱导的神经元细胞表达各种神经元特异性蛋白，它们在神经元分化过程中的 mRNA 表达重现了胚胎神经发生，它们产生动作电位，并在体外形成功能性突触。此外，将 iMuSCs 或其细胞提取物移植到 mdx 小鼠（即杜氏肌营养不良症 [DMD] 的小鼠模型）的肌肉中，可以恢复其先前受损的神经肌肉接头（NMJ）的形态，这表明 iMuSCs 的有益作用不仅限于细胞修复，还可能与其短暂的旁分泌作用有关。本研究揭示了 iMuSCs 在与损伤和疾病相关的 NMJ 修复中的重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f89/5430871/5383d3cd34cb/41598_2017_1311_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f89/5430871/5383d3cd34cb/41598_2017_1311_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f89/5430871/548c3e587c72/41598_2017_1311_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f89/5430871/aa5635d04c49/41598_2017_1311_Fig2_HTML.jpg
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