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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Sustained delivery of erythropoietin in mice by genetically modified skin fibroblasts.
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Sustained delivery of erythropoietin in mice by genetically modified skin fibroblasts.

机译：基因修饰的皮肤成纤维细胞在小鼠中持续释放促红细胞生成素。

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摘要

We have examined whether the secretion of erythropoietin (Epo) from genetically modified cells could represent an alternative to repeated injections of the recombinant hormone for treating chronic anemias responsive to Epo. Primary mouse skin fibroblasts were transduced with a retroviral vector in which the murine Epo cDNA is expressed under the control of the murine phosphoglycerate kinase promoter. "Neo-organs" containing the genetically modified fibroblasts embedded into collagen lattices were implanted into the peritoneal cavity of mice. Increased hematocrit (> 80%) and elevated serum Epo concentration (ranging from 60 to 408 milliunits/ml) were observed in recipient animals over a 10-month observation period. Hematocrit values measured in recipient mice varied according to the number of implanted Epo-secreting fibroblasts (ranging from 2.5 to 20 x 10(6)). The implantation of neo-organs containing Epo-secreting fibroblasts appeared, therefore, as a convenient method to achieve permanent in vivo delivery of the hormone. We estimated that the biological efficacy of the approach may be relevant for the treatment of human hemoglobinopathies.
机译：我们已经检查了转基因细胞中促红细胞生成素（Epo）的分泌是否可以代表重复注射重组激素来治疗对Epo的慢性贫血的替代方法。用逆转录病毒载体转导原代小鼠皮肤成纤维细胞，其中在鼠磷酸甘油酸酯激酶启动子的控制下表达鼠Epo cDNA。将含有嵌入胶原蛋白晶格中的转基因成纤维细胞的“新器官”植入小鼠的腹膜腔中。在10个月的观察期内，在受体动物中观察到血细胞比容升高（> 80％）和血清Epo浓度升高（范围从60到408毫单位/毫升）。在受体小鼠中测得的血细胞比容值根据植入的分泌Epo的成纤维细胞的数量而变化（范围从2.5到20 x 10（6））。因此，出现了含有分泌Epo的成纤维细胞的新器官的植入，作为实现体内永久性递送激素的方便方法。我们估计该方法的生物学功效可能与人类血红蛋白病的治疗有关。

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