Extended amplification in vitro and replicative senescence:: Key factors implicated in the success of human myoblast transplantation
Extended amplification in vitro and replicative senescence:: Key factors implicated in the success of human myoblast transplantation
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DOI：
10.1089/104303403322168000
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发表时间：
2003-08-01
影响因子：
4.2
通讯作者：
Mouly, V
中科院分区：
文献类型：
--
作者：
Cooper, RN;Thiesson, D;Mouly, V
人成肌细胞移植的有限成功与移植后的免疫排斥、存活率差和注射的成肌细胞的有限扩散有关。一个重要的问题，很少受到关注，但在成肌细胞移植方案的根本重要性，是人卫星细胞的增殖能力。我们实验室以前的研究表明，卫星细胞群体在生命的前二十年中可以进行的最大分裂次数随着年龄的增长而减少，然后在成年期稳定下来。这些观察结果表明，当卫星细胞作为载体在成肌细胞移植方案中，重要的是要考虑供体年龄和细胞在移植前分裂的数量作为限制因素，以获得最佳数量的供体来源的肌纤维。在这项研究中，来自不同年龄（新生儿，17岁，和71岁）的捐助者的成肌细胞分离和扩增培养。在植入后第4周和第8周，评价了它们在RAG 2（-/-）/γ（c）/C5三重免疫缺陷宿主中参与体内肌肉再生的潜力。我们的研究结果表明，在文化中的长期扩增和复制衰老的方法都是重要的因素，可能条件成肌细胞移植方案的成功。
The limited success of human myoblast transplantation has been related to immune rejection, poor survival, and limited spread of injected myoblasts after transplantation. An important issue that has received little attention, but is nevertheless of fundamental importance in myoblast transplantation protocols, is the proliferative capacity of human satellite cells. Previous studies from our laboratory have demonstrated that the maximum number of divisions that a population of satellite cells can make decreases with age during the first two decades of life then stabilizes in adulthood. These observations indicate that when satellite cells are used as vectors in myoblast transplantation protocols it is important to consider donor age and the number of divisions that the cells have made prior to transplantation as limiting factors in obtaining an optimal number of donor derived muscle fibers. In this study, myoblasts derived from donors of different ages ( newborn, 17 years old, and 71 years old) were isolated and amplified in culture. Their potential to participate in in vivo muscle regeneration in RAG2(-/-)/gamma(c)/C5 triple immunodeficient hosts after implantation was evaluated at 4 and 8 weeks postimplantation. Our results demonstrate that prolonged amplification in culture and the approach to replicative senescence are both important factors that may condition the success of myoblast transplantation protocols.