Endothelial progenitor cell-based therapy for hemophilia A
Endothelial progenitor cell-based therapy for hemophilia A
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DOI：
10.1007/s12185-012-1015-z
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发表时间：
2012-02-01
影响因子：
2.1
通讯作者：
Matsui, Hideto
中科院分区：
文献类型：
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作者：
Matsui, Hideto
过去几十年的临床前和临床研究结果表明，建立一种有效和成功的血友病A基因治疗的目标仍然是可行和现实的。然而，目前还没有任何单一的办法被证明是明显优越的，一些反复出现的挑战仍有待克服。考虑到宿主对系统体内基因传递的免疫反应持续存在的问题，以及转基因传递和表达不足的额外障碍，我们建议重新评估利用转基因干细胞群体的体外基因转移方法。在这一策略中，从血友病动物中获得自体血生长内皮祖细胞，通过工程病毒将第八因子基因的正常拷贝导入其中。在人工开发的支持环境中，在血友病动物的皮肤下重新植入细胞之前，细胞数量在培养中扩大。治疗的后续评估包括凝血活性的一般评估、血液中第八因子水平的具体测量和临床观察。
As shown by the results of both pre-clinical and clinical studies reported in past decades, the goal of establishing an effective and successful gene therapy for hemophilia A remains feasible and realistic. However, at this time, no single approach has been shown to be clearly superior, and a number of recurring challenges remain to be overcome. Given the persistent problems presented by the host immune response to systemic in vivo gene delivery, and the additional obstacles of inadequate transgene delivery and expression, we propose a re-evaluation of an ex vivo gene transfer approach that utilizes a genetically modified stem cell population. In this strategy, autologous blood outgrowth endothelial progenitor cells are obtained from hemophilic animals, into which a normal copy of the factor VIII gene is introduced via an engineered virus. Cell numbers are expanded in culture prior to their re-implantation under the skin of the hemophilic animals in an artificially developed supporting environment. Follow-up assessment of the treatment involves the general evaluation of clotting activity, the specific measurement of factor VIII levels in the blood, and clinical observation.