contribution of human muscle-derived cells to skeletal muscle regeneration in dystrophic host mice的贡献人类肌源性细胞在瘠薄主机小鼠骨骼肌的再生.pdf

Contribution of Human Muscle-Derived Cells to Skeletal Muscle Regeneration in Dystrophic Host Mice 1 1 2 1 1 Jinhong Meng , Carl F. Adkin , Shi-wen Xu , Francesco Muntoni , Jennifer E. Morgan * 1The Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, United Kingdom, 2 Centre for Rheumatology, Department of Medicine, University College London - Royal Free Campus, London, United Kingdom Abstract Background: 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. Methodology/Principal 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. Conclusions/Significance: Our data complement and extend previous findings on human skeletal muscle-d