Skeletal muscle differentiation potential of human adult bone marrow cells

Skeletal muscle differentiation potential of human adult bone marrow cells
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DOI:
10.1016/j.yexcr.2003.12.015
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发表时间:
2004-04-15
影响因子:
3.7
通讯作者:
Soligo, D
Soligo, D
中科院分区:
医学3区
文献类型:
--
作者:
Bossolasco, P;Corti, S;Soligo, D

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小鼠骨髓(BM)细胞在不同的肌肉再生模型中经历了肌源性、分化和参与肌肉修复。在这篇论文中,我们报告了在成人骨髓中具有肌源性潜能的一个亚群(CD45+/desmin+)。通过一种简单的培养方法,我们能够在体外获得高达20%的多核肌管。肌管是用从开胸手术中获得的肋骨碎片冲洗的BM和从髂骨抽吸物中提取的BM生成的。通过免疫细胞化学、实时RT-PCR、流式细胞术和Western印迹分析,不同贴壁和非贴壁部分的细胞表达大量的肌肉特异性标记。此外,将完整的骨髓直接注射到免疫缺陷小鼠的右侧胫骨前肌(NOD/RAG)中,显示出不同但显著的人类细胞植入水平(从0.06%到0.26%Dys+/FISH+纤维)。这些结果表明,成人骨髓中存在具有骨骼肌分化潜能的细胞,在免疫缺陷小鼠肌肉损伤后,可以在体外分化并在体内产生肌源性细胞。进一步的改进可能会为肌肉疾病的细胞介导治疗提供新的方法。(C)2004 Elsevier Inc.保留所有权利。
Murine bone marrow (BM) cells have been shown to undergo myogenic, differentiation and participate in muscle repair in different muscle regeneration models. In the present paper, we report on a subset of cells (CD45+/desmin+) with myogenic potential being present at very low frequencies in human adult BM. By a simple culture method, we were able to obtain in vitro multinucleated myotubes in up to 20% of the cultures. Myotubes were generated using both BM flushed from rib fragments obtained during thoracotomy and BM derived from iliac crest aspirates. Cells of the different adherent and non-adherent fractions expressed numerous muscle specific markers by immunocytochemistry, real-time RT-PCR, flow cytometry, and Western blot analyses. Moreover, direct injection of whole BM into the right tibialis anterior muscle of inummodeficient mice (NOD/RAG) that had previously been treated with cardiotoxin to induce muscle degeneration, showed a variable but significant level of human cell engraftment (from 0.06 to 0.26% Dys+/FISH+ fibers). These data suggest that cells with skeletal muscle differentiation potential are present in adult human BM can differentiate in vitro and give rise to myogenic cells in vivo in immunodeficient mice after muscle damage. Further improvements might allow new approaches to cell-mediated therapies for muscular diseases. (C) 2004 Elsevier Inc. All rights reserved.