Bone marrow derived cells in adult skeletal muscle tissue in humans.
Bone marrow derived cells in adult skeletal muscle tissue in humans.
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DOI：
10.1186/2044-5040-3-12
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发表时间：
2013-05-16
期刊：
影响因子：
4.9
通讯作者：
Gustafsson T
中科院分区：
文献类型：
--
作者：
Strömberg A;Jansson M;Fischer H;Rullman E;Hägglund H;Gustafsson T
在过去的十年中，一些动物研究表明，除了局部细胞外，来自骨髓的细胞（BM）还具有促进受伤骨骼肌组织再生的能力。此外，在小鼠中，有规律的体育活动已被证明对脑基细胞对肌肉的贡献有足够的刺激，表明这是骨骼肌正在进行的生理重塑的一部分。然而，bm来源的细胞是否参与人类骨骼肌重塑尚不清楚。为此，我们分析了移植男性骨髓的女性健康人骨骼肌中BM来源细胞的掺入情况。对6 ~ 12年前接受男性供体造血干细胞移植的女性股外侧肌进行骨骼肌活检。健康女性作为对照。骨骼肌纤维、卫星细胞（SCs）或内皮细胞（ECs）的免疫组织化学染色结合X和Y染色体的荧光原位杂交（FISH）来鉴定活检组织中BM来源的细胞。三维共聚焦成像证实了Y染色体和DAPI在肌纤维中的共定位。为了进一步研究bm来源的细胞是否融入SC生态位，从移植妇女的活检中提取成肌细胞，培养并使用XY FISH和免疫细胞化学分析。三维共聚焦成像无可争议地证明了Y染色体和DAPI在肌纤维中的共定位。一些Y染色体位于细胞核中心。在CD56+ SCs的组织切片和从提取的SCs培养的成肌细胞中未检测到Y染色体。移植体各切片均可见Y染色体+ ECs。在健康对照妇女的骨骼肌活检中未发现Y染色体。我们证明脑脊髓瘤来源的细胞有助于骨骼肌纤维和内皮细胞。我们的研究结果支持BM对骨骼肌的贡献是通过与肌肉纤维的直接融合发生的，并且贡献细胞来自造血谱系。因此，目前的发现鼓励进一步研究这一过程在整个生命中发生的生理适应的重要性。
During the past decade, several animal studies have demonstrated that in addition to local cells, cells from the bone marrow (BM) possess the ability to contribute to regeneration of injured skeletal muscle tissue. In addition, in mice, regular physical activity has been displayed to be a sufficient stimulus for BM-derived cell contribution to the muscle, indicating that this is part of the ongoing physiological remodeling of skeletal muscle. However, whether BM-derived cells participate in human skeletal muscle remodeling is not known. To this end, we analyzed the incorporation of BM-derived cells in healthy human skeletal muscle in women transplanted with male BM. Skeletal muscle biopsies were obtained from the m. vastus lateralis of women transplanted with male donor hematopoietic stem cells 6 to 12 years earlier. Healthy women served as controls. Immunohistochemical staining for skeletal muscle fibers, satellite cells (SCs) or endothelial cells (ECs) combined with fluorescent in situ hybridization (FISH) of X and Y chromosomes was used to identify cells of BM origin within the biopsies. Three dimensional confocal imaging was performed to demonstrate colocalization of Y chromosome and DAPI within muscle fibers. To further investigate whether BM-derived cells incorporate into the SC niche, myoblasts were extracted from the biopsies from the transplanted women, cultured, and analyzed using XY FISH and immunocytochemistry. Three dimensional confocal imaging indisputably demonstrated colocalization of Y chromosome and DAPI within muscle fibers. Some Y chromosomes were found within centrally located nuclei. No Y chromosomes were detected in CD56+ SCs in the tissue sections nor in the myoblasts cultured from the extracted SCs. Y chromosome+ ECs were found in all sections from the transplanted subjects. No Y chromosomes were found in the skeletal muscle biopsies obtained from healthy control women. We demonstrate that BM-derived cells contribute to skeletal muscle fibers and ECs. Our results support that BM contribution to skeletal muscle occurs via direct fusion to muscle fibers, and that the contributing cells derive from the hematopoietic lineage. Thus, the present findings encourage further studies of the importance of this process for the physiological adaptation occurring throughout life.
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