Specific adeno-associated virus serotypes facilitate efficient gene transfer into human and non-human primate mesenchymal stromal cells
Specific adeno-associated virus serotypes facilitate efficient gene transfer into human and non-human primate mesenchymal stromal cells
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DOI：
10.1002/jgm.990
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发表时间：
2007-01-01
影响因子：
3.5
通讯作者：
Rasko, John E. J.
中科院分区：
文献类型：
--
作者：
Chng, Keefe;Larsen, Stephen R.;Rasko, John E. J.
间充质基质细胞（MSCs）在体外基因和细胞介导的治疗中显示出巨大的潜力。原代狒狒间充质干细胞的免疫表型和体外分化能力被证明与在人间充质干细胞中观察到的几乎相同。为了优化基因转移效率，我们比较了血清型1、2、3、4、5、6和8的腺相关病毒（AAV）载体介导人和狒狒MSC转导的能力的效率。AAV血清型2载体在转导来自人和狒狒的MSC中是最有效的。作为参考，用这七种AAV血清型转导人Ad 293细胞，并且发现具有最高的转导水平，其次是狒狒MSC，然后是人MSC。测试的血清型的增加转导效率的顺序对于人和狒狒MSC是相似的，但是对于人Ad 293细胞是不同的。从不同个体分离的MSC的转导效率在相同物种内是相当的。我们还证明了用AAV血清型2载体转导的狒狒MSC保留了它们在体外分化成脂肪细胞的潜力，并且可以在体内掺入NODSCID小鼠的损伤肌肉组织中。在这项研究中，我们检测到β-半乳糖苷酶报告基因在宿主肌肉组织中的表达长达9周，表明转导的狒狒MSC的植入和体内持续的转基因表达。版权所有（c）2006约翰威利父子有限公司。
Mesenchymal stromal cells (MSCs) show great promise for ex vivo gene and cell-mediated therapies. The immunophenotype and in vitro differentiation capacity of primary baboon MSCs was demonstrated to be near-identical to that observed in human MSCs. To optimize gene transfer efficiency, we compared the efficiency of serotypes 1, 2, 3, 4, 5, 6, and 8 of adeno-associated virus (AAV) vectors for their ability to mediate transduction of human and baboon MSCs. AAV serotype 2 vectors were the most efficient in transducing MSCs from humans and baboons. As a reference, human Ad293 cells were transduced with these seven AAV serotypes, and were found to have the highest transduction levels followed by baboon MSCs, and then human MSCs. The order of increasing transduction efficiency for the serotypes tested was similar for human and baboon MSCs, but was different for human Ad293 cells. The transduction efficiency of MSCs isolated from different individuals was comparable within the same species. We also demonstrated that baboon MSCs transduced with AAV serotype 2 vectors retain their potential to differentiate into adipocytes in vitro, and can incorporate into injured muscle tissue of NODSCID mice in vivo. We detected beta-galactosidase reporter gene expression in host muscle tissue for up to 9 weeks in this study, indicating engraftment of transduced baboon MSCs and sustained transgene expression in vivo. Copyright (c) 2006 John Wiley & Sons, Ltd.