Gene delivery by the hSP-B promoter to lung alveolar type II epithelial cells in LAL-knockout mice through bone marrow mesenchymal stem cells
Gene delivery by the hSP-B promoter to lung alveolar type II epithelial cells in LAL-knockout mice through bone marrow mesenchymal stem cells
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DOI：
10.1038/sj.gt.3303006
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发表时间：
2007-10-01
期刊：
影响因子：
5.1
通讯作者：
Du, H.
中科院分区：
文献类型：
--
作者：
Yan, C.;Lian, X.;Du, H.
组织损伤和炎症促使骨髓干细胞(BMSCs)在驻留组织中分化为多种细胞类型。骨髓间充质干细胞可以稳定地保持其可塑性，是将治疗基因输送到非造血组织的理想细胞群。我们以LacZ为报告基因，通过β-半乳糖苷酶染色、流式细胞术和双重免疫荧光染色，证明了肺特异性人表面活性蛋白B(HSP-B)1.5-kb启动子能够将LacZ基因带入溶酶体酸性脂肪酶(Lal-/-)基因敲除小鼠的肺内。在受体LAL-/-小鼠体内，BMSC注射8周后，约有10-18%的肺泡II型上皮细胞(AT-II细胞)呈LacZ基因阳性表达。野生型小鼠在同样的处理后没有表现出任何表达。来自HSP-B 1.5-kb LacZ转基因小鼠的骨髓间充质干细胞进入并在Lal-/-骨髓中再生。这项研究支持LAL缺乏引起的肺部炎症可以触发BMSC停留在LAL/骨髓，迁移到肺并转化为AT II细胞的概念。HSP-B 1.5kb启动子是通过骨髓间充质干细胞将治疗性基因导入AT II细胞治疗肺部炎症性疾病的理想工具。
Tissue damage and inflammation promote bone marrow stem cells (BMSCs) to differentiate into a variety of cell types in residing tissues. BMSCs can stably maintain their plasticity and are an ideal cell population for delivery of therapeutic genes to non-hematopoietic tissues. Using lacZ as a reporter gene, we demonstrated that the lung-specific human surfactant protein B (hSP-B) 1.5-kb promoter is able to deliver the lacZ gene into the lung of lysosomal acid lipase (LAL) gene-knockout (lal-/-) mice by beta-galactosidase staining, flow cytometry and double immunofluorescence staining. Around 10-18% alveolar type II epithelial cells (AT II cells) exhibited positive lacZ gene expression after 8 weeks of BMSC injection in recipient lal-/-mice. The wild-type mice exhibited no expression after the same treatment. BMSCs from hSP-B 1.5-kb lacZ transgenic mice entered and repopulated in lal-/-bone marrow. The study supports a concept that pulmonary inflammation caused by LAL deficiency can trigger BMSC residing in lal-/-bone marrow, migrating into the lung and converting into residential AT II cells. The hSP-B 1.5 kb promoter is an ideal tool to deliver therapeutic genes into AT II cells through BMSCs to cure pulmonary inflammation-triggered diseases.