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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 Therapy volume 14, pages 1461–1470 (2007)Cite this article

Abstract

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 β-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.

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Acknowledgements

This study was supported by National Institute of Health Grants HL-061803 and HL-067862 (C Yan and H Du). We thank Ms Marjorie Albrecht for critical reading of this manuscript.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, The Center for Immunobiology, Indiana University School of Medicine, Indianapolis, IN, USA

    C Yan, Y Dai, X Wang & P Qu

  2. Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA

    X Lian, A White, Y Qin & H Du

  3. Department of Pathology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    C Yan & X Wang

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  1. C Yan
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  2. X Lian
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  7. Y Qin
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Correspondence to C Yan or H Du.

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Supplementary Information accompanies the paper on Gene Therapy website (http://www.nature.com/gt)

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Yan, C., Lian, X., Dai, Y. et al. 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 Ther 14, 1461–1470 (2007). https://doi.org/10.1038/sj.gt.3303006

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  • DOI: https://doi.org/10.1038/sj.gt.3303006

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