Transplanted primary neonatal myoblasts can give rise to functional satellite cells as identified using the Myf5nlacZ/+ mouse
Transplanted primary neonatal myoblasts can give rise to functional satellite cells as identified using the Myf5nlacZ/+ mouse
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DOI：
10.1038/sj.gt.3301463
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发表时间：
2001-05-01
期刊：
影响因子：
5.1
通讯作者：
Zammit, PS
中科院分区：
文献类型：
--
作者：
Heslop, L;Beauchamp, JR;Zammit, PS
成肌细胞移植是一种潜在的骨骼肌组织遗传修饰治疗方法。然而，要被认为是一种有效的、长寿命的递送方法，必须至少有一部分移植的细胞也保留其增殖潜力。我们试图调查是否移植新生成肌细胞可以通过使用Myf 5（nlacZ/+）小鼠的成年骨骼肌的卫星细胞室。Myf 5（nlacZ/+）小鼠具有靶向Myf 5基因座的nlacZ，导致静止卫星细胞中的β-半乳糖苷酶活性。移植后，在宿主肌肉中检测到β-半乳糖苷酶标记的细胞核，表明供体细胞已被掺入。值得注意的是，β-半乳糖苷酶阳性，因此供体来源的卫星细胞被检测到。当置于培养物中时，β-半乳糖苷酶标记的肌源性细胞从母体纤维发出。这些观察结果表明，细胞移植不仅导致供体细胞核并入宿主肌肉合胞体，而且供体细胞可以成为功能性卫星细胞。因此，Myf 5（nlacZ/+）小鼠提供了用于确定移植细胞对卫星细胞池的贡献的新的和特异性的标记物。
Myoblast transplantation is a potential therapeutic approach for the genetic modification of host skeletal muscle tissue. To be considered an effective, long-lived method of delivery, however, it is essential that at least a proportion of the transplanted cells also retain their proliferative potential. We sought to investigate whether transplanted neonatal myoblasts can contribute to the satellite cell compartment of adult skeletal muscle by using the Myf5(nlacZ/+) mouse. The Myf5(nlacZ/+) mouse has nlacZ targeted to the Myf5 locus resulting in beta -galactosidase activity in quiescent satellite cells. Following transplantation, beta -galactosidase-labelled nuclei were detected in host muscles, showing that donor cells had been incorporated. Significantly, beta -galactosidase-positive, and therefore donor-derived, satellite cells were detected When placed in culture, beta -galactosidase marked myogenic cells emanated from the parent fibre. These observations demonstrate that cell transplantation not only results in the incorporation of donor nuclei into the host muscle syncytia, but also that the donor cells can become functional satellite cells. The Myf5(nlacZ/+) mouse therefore provides a novel and specific marker for determining the contribution of transplanted cells to the satellite cell pool.