Marrow-derived cells as vehicles for delivery of gene therapy to pulmonary epithelium
Marrow-derived cells as vehicles for delivery of gene therapy to pulmonary epithelium
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DOI：
10.1165/rcmb.2002-0056rc
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发表时间：
2002-12-01
影响因子：
6.4
通讯作者：
Krause, DS
中科院分区：
文献类型：
--
作者：
Grove, JE;Lutzko, C;Krause, DS
基因治疗在肺气道和肺泡腔中的应用为肺部疾病的治疗带来了巨大的希望。然而，使用病毒和非病毒载体安全有效的长期基因表达尚未实现。腺病毒载体对气道上皮具有天然亲和力，已部分有效，但具有炎症性并且仅诱导瞬时基因表达。我们研究了使用逆转录病毒转导的多能骨髓干细胞（BMSC）向肺上皮进行基因治疗的新方法。我们之前已经证明，BMSC 移植后高达 20% 的肺上皮细胞可以来自骨髓。在这里，受辐射的雌性小鼠被移植了用编码 eGFP 的逆转录病毒转染的雄性骨髓。移植后 2、5 或 11 个月分析的所有受体中都存在表达转基因的肺上皮细胞（n = 10），这表明高度可塑性的 BMSC 可以在体外稳定转染，并保留其分化为肺上皮的能力，同时维持长期转基因表达。
Gene therapy application to pulmonary airways and alveolar spaces holds tremendous promise for the treatment of lung diseases. However, safe and effective long-term gene expression using viral and nonviral vectors has not yet been achieved. Adenoviral vectors, with a natural affinity for airway epithelia, have been partially effective, but are inflammatory and induce only transient gene expression. We investigate the novel approach of using retrovirally transduced multipotent bone marrow-derived stem cells (BMSC) to deliver gene therapy to lung epithelium. We have shown previously that up to 20% of lung epithelial cells can be derived from marrow following BMSC transplantation. Here, irradiated female mice were transplanted with male marrow that had been transcluced with retrovirus encoding eGFP. Transgene expressing lung epithelial cells were present in all recipients analyzed at 2, 5, or 11 mo after transplant (n = 10), demonstrating that highly plastic BMSC can be stably transcluced in vitro and retain their ability to differentiate into lung epithelium while maintaining long-term transgene expression.