Dellavalle Arianna, Sampaolesi Maurilio, Tonlorenzi Rossana, Tagliafico Enrico, Sacchetti Benedetto, Perani Laura, Innocenzi Anna, Galvez Beatriz G, Messina Graziella, Morosetti Roberta, Li Sheng, Belicchi Marzia, Peretti Giuseppe, Chamberlain Jeffrey S, Wright Woodring E, Torrente Yvan, Ferrari Stefano, Bianco Paolo, Cossu Giulio
Stem Cell Research Institute, San Raffaele Scientific Institute, 58 Via Olgettina, 20132 Milan, Italy.
Nat Cell Biol. 2007 Mar;9(3):255-67. doi: 10.1038/ncb1542. Epub 2007 Feb 11.
Cells derived from blood vessels of human skeletal muscle can regenerate skeletal muscle, similarly to embryonic mesoangioblasts. However, adult cells do not express endothelial markers, but instead express markers of pericytes, such as NG2 proteoglycan and alkaline phosphatase (ALP), and can be prospectively isolated from freshly dissociated ALP(+) cells. Unlike canonical myogenic precursors (satellite cells), pericyte-derived cells express myogenic markers only in differentiated myotubes, which they form spontaneously with high efficiency. When transplanted into severe combined immune deficient-X-linked, mouse muscular dystrophy (scid-mdx) mice, pericyte-derived cells colonize host muscle and generate numerous fibres expressing human dystrophin. Similar cells isolated from Duchenne patients, and engineered to express human mini-dystrophin, also give rise to many dystrophin-positive fibres in vivo. These data show that myogenic precursors, distinct from satellite cells, are associated with microvascular walls in the human skeletal muscle, may represent a correlate of embryonic 'mesoangioblasts' present after birth and may be a promising candidate for future cell-therapy protocols in patients.
源自人类骨骼肌血管的细胞能够再生骨骼肌,这与胚胎期的中血管成肌细胞类似。然而,成体细胞不表达内皮标志物,而是表达周细胞标志物,如NG2蛋白聚糖和碱性磷酸酶(ALP),并且可以从新鲜解离的ALP(+)细胞中前瞻性地分离出来。与典型的成肌前体细胞(卫星细胞)不同,周细胞衍生细胞仅在分化的肌管中表达成肌标志物,它们能高效自发地形成这些肌管。当将周细胞衍生细胞移植到重症联合免疫缺陷-X连锁小鼠肌营养不良症(scid-mdx)小鼠体内时,这些细胞会在宿主肌肉中定植,并产生大量表达人抗肌萎缩蛋白的纤维。从杜兴氏症患者中分离出的类似细胞,经工程改造后表达人微小抗肌萎缩蛋白,在体内也能产生许多抗肌萎缩蛋白阳性纤维。这些数据表明,与卫星细胞不同的成肌前体细胞与人类骨骼肌的微血管壁相关,可能代表出生后存在的胚胎“中血管成肌细胞”的一种对应物,并且可能是未来患者细胞治疗方案的一个有前景的候选者。