Contribution of human muscle-derived cells to skeletal muscle regeneration in dystrophic host mice.
Contribution of human muscle-derived cells to skeletal muscle regeneration in dystrophic host mice.
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DOI：
10.1371/journal.pone.0017454
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发表时间：
2011-03-09
期刊：
影响因子：
3.7
通讯作者：
Morgan JE
中科院分区：
文献类型：
--
作者：
Meng J;Adkin CF;Xu SW;Muntoni F;Morgan JE
干细胞移植是肌营养不良症的一种有希望的潜在疗法，但为此目的，细胞需要是可全身递送的，产生许多肌纤维，并在大多数患者骨骼肌中功能性地重建卫星细胞龛。人骨骼肌来源的周细胞已被证明在肌营养不良蛋白缺陷的宿主小鼠中动脉内移植后形成肌纤维。我们的目标是复制和扩展这些有希望的发现。人肌源性细胞（mdc）的分离和维持如公开的人周细胞进行。通过免疫组化、流式细胞术和RT-PCR对骨髓间充质干细胞进行鉴定，并检测其体外分化为肌管和体内分化为肌纤维的能力。尽管人mdc和周细胞之间存在微小差异，但mdc在mdx nu/nu小鼠肌肉内注射后有助于肌肉再生，CD 56+亚群尤其是肌源性的。然而，与mdx SCID宿主中动脉内递送的人周细胞相反，mdscs在mdx nu/nu宿主中全身递送后不有助于肌肉再生。我们的数据补充和扩展了以前对人骨骼肌源性干细胞的研究结果，并清楚地表明，需要进一步的工作来制备来自骨骼肌的纯细胞群，这些细胞群在培养中保持其表型，并在营养不良小鼠模型中全身递送后对骨骼肌再生做出强大的贡献。协议，动物模型或结果测量的微小差异可能是我们的研究结果与以前的数据之间存在差异的原因，但仍然强调需要对肌源性干细胞进行更详细的研究，并在临床试验中使用这些细胞之前独立复制结果。
Stem cell transplantation is a promising potential therapy for muscular dystrophies, but for this purpose, the cells need to be systemically-deliverable, give rise to many muscle fibres and functionally reconstitute the satellite cell niche in the majority of the patient's skeletal muscles. Human skeletal muscle-derived pericytes have been shown to form muscle fibres after intra-arterial transplantation in dystrophin-deficient host mice. Our aim was to replicate and extend these promising findings. Isolation and maintenance of human muscle derived cells (mdcs) was performed as published for human pericytes. Mdscs were characterized by immunostaining, flow cytometry and RT-PCR; also, their ability to differentiate into myotubes in vitro and into muscle fibres in vivo was assayed. Despite minor differences between human mdcs and pericytes, mdscs contributed to muscle regeneration after intra-muscular injection in mdx nu/nu mice, the CD56+ sub-population being especially myogenic. However, in contrast to human pericytes delivered intra-arterially in mdx SCID hosts, mdscs did not contribute to muscle regeneration after systemic delivery in mdx nu/nu hosts. Our data complement and extend previous findings on human skeletal muscle-derived stem cells, and clearly indicate that further work is necessary to prepare pure cell populations from skeletal muscle that maintain their phenotype in culture and make a robust contribution to skeletal muscle regeneration after systemic delivery in dystrophic mouse models. Small differences in protocols, animal models or outcome measurements may be the reason for differences between our findings and previous data, but nonetheless underline the need for more detailed studies on muscle-derived stem cells and independent replication of results before use of such cells in clinical trials.
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