Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells
Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells
复制标题
DOI：
10.1038/ncb1542
复制
发表时间：
2007-03-01
影响因子：
21.3
通讯作者：
Cossu, Giulio
中科院分区：
文献类型：
--
作者：
Dellavalle, Arianna;Sampaolesi, Maurilio;Cossu, Giulio
来源于人骨骼肌血管的细胞可以再生骨骼肌，类似于胚胎中成血管细胞。然而，成年细胞不表达内皮标记物，而是表达周细胞标记物，例如NG 2蛋白聚糖和碱性磷酸酶（ALP），并且可以从新鲜分离的ALP（+）细胞中前瞻性地分离。与典型的肌源性前体细胞（卫星细胞）不同，周细胞衍生的细胞仅在分化的肌管中表达肌源性标记物，它们自发地以高效率形成。当移植到严重的联合免疫缺陷-X-连锁，小鼠肌营养不良症（scid-mdx）小鼠，周细胞衍生的细胞定殖宿主肌肉，并产生大量的纤维表达人肌营养不良蛋白。从杜氏病患者中分离的类似细胞，经工程改造以表达人微型肌营养不良蛋白，也在体内产生许多肌营养不良蛋白阳性纤维。这些数据表明，肌源性前体细胞，不同于卫星细胞，与人骨骼肌中的微血管壁相关，可能代表出生后存在的胚胎“mesoangioblasts”的相关性，并可能是未来患者细胞治疗方案的有希望的候选者。
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.