Clonal isolation of muscle-derived cells capable of enhancing muscle regeneration and bone healing.

Clonal isolation of muscle-derived cells capable of enhancing muscle regeneration and bone healing.
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DOI:
10.1083/jcb.150.5.1085
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发表时间:
2000-09-04
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Huard J
Huard J
中科院分区:
其他
文献类型:
--
作者:
Lee JY;Qu-Petersen Z;Cao B;Kimura S;Jankowski R;Cummins J;Usas A;Gates C;Robbins P;Wernig A;Huard J

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最近的几项研究表明,骨骼肌中的干细胞的分离,但这些肌肉来源的干细胞的功能特性仍然不清楚。在本研究中,我们报告的纯化肌肉来源的干细胞从mdx小鼠,动物模型杜氏肌营养不良症。我们表明,富集结蛋白+细胞使用预培养技术从小鼠原代肌肉细胞培养也丰富了表达CD 34和Bcl-2的细胞群。结果发现,在基底层中存在CD 34+细胞和Bcl-2+细胞,从这些富含CD 34 +Bcl-2+细胞的细胞群中克隆分离并鉴定出一种肌源性干细胞mc 13,该细胞在体外和体内均能分化为肌源性和成骨细胞系。mc 13细胞是c-kit和CD 45阴性的,并表达:结蛋白,c-met和MNF,在早期肌原性祖细胞中表达的三种标志物; Flk-1,最近在人类中鉴定为具有干细胞样特征的造血细胞中的关键标志物的KDR的小鼠同源物;和Sca-1,骨骼肌和造血干细胞的标志物。肌肉内,更重要的是,静脉注射mc 13细胞导致mdx小鼠肌肉再生和肌营养不良蛋白的部分恢复。mc 13细胞移植分泌成骨蛋白,分化成骨细胞系,促进严重联合免疫缺陷小鼠颅骨缺损愈合。总之,这些结果表明分离出了一群能够改善肌肉再生和骨愈合的肌肉源性干细胞。
Several recent studies suggest the isolation of stem cells in skeletal muscle, but the functional properties of these muscle-derived stem cells is still unclear. In the present study, we report the purification of muscle-derived stem cells from the mdx mouse, an animal model for Duchenne muscular dystrophy. We show that enrichment of desmin+ cells using the preplate technique from mouse primary muscle cell culture also enriches a cell population expressing CD34 and Bcl-2. The CD34+ cells and Bcl-2+ cells were found to reside within the basal lamina, where satellite cells are normally found. Clonal isolation and characterization from this CD34+Bcl-2+ enriched population yielded a putative muscle-derived stem cell, mc13, that is capable of differentiating into both myogenic and osteogenic lineage in vitro and in vivo. The mc13 cells are c-kit and CD45 negative and express: desmin, c-met and MNF, three markers expressed in early myogenic progenitors; Flk-1, a mouse homologue of KDR recently identified in humans as a key marker in hematopoietic cells with stem cell-like characteristics; and Sca-1, a marker for both skeletal muscle and hematopoietic stem cells. Intramuscular, and more importantly, intravenous injection of mc13 cells result in muscle regeneration and partial restoration of dystrophin in mdx mice. Transplantation of mc13 cells engineered to secrete osteogenic protein differentiate in osteogenic lineage and accelerate healing of a skull defect in SCID mice. Taken together, these results suggest the isolation of a population of muscle-derived stem cells capable of improving both muscle regeneration and bone healing.
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发表时间: 1999-05-01
期刊: ANATOMY AND EMBRYOLOGY
影响因子: --
作者:
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期刊: CYTOGENETICS
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影响因子: 7.8
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发表时间: 1994-08-01
期刊: HUMAN GENE THERAPY
影响因子: 4.2
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