Gene delivery by the hSP-B promoter to lung alveolar type II epithelial cells in LAL-knockout mice through bone marrow mesenchymal stem cells

C. Yan, X. Lian, Y. Dai, X. Wang, P. Qu, A. White, Y. Qin, H. Du

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 1.5kb promoter is an ideal tool to deliver therapeutic genes into AT II cells through BMSCs to cure pulmonary inflammation-triggered diseases.

Original languageEnglish (US)
Pages (from-to)1461-1470
Number of pages10
JournalGene Therapy
Volume14
Issue number20
DOIs
StatePublished - Oct 1 2007

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Sterol Esterase
Alveolar Epithelial Cells
Mesenchymal Stromal Cells
Knockout Mice
Surface-Active Agents
Bone Marrow Cells
Stem Cells
Bone Marrow
Lung
Genes
Lac Operon
Pneumonia
Galactosidases
Staining and Labeling
Gene Knockout Techniques
Reporter Genes
Transgenic Mice
Fluorescent Antibody Technique
IgA receptor
Flow Cytometry

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Gene delivery by the hSP-B promoter to lung alveolar type II epithelial cells in LAL-knockout mice through bone marrow mesenchymal stem cells. / Yan, C.; Lian, X.; Dai, Y.; Wang, X.; Qu, P.; White, A.; Qin, Y.; Du, H.

In: Gene Therapy, Vol. 14, No. 20, 01.10.2007, p. 1461-1470.

Research output: Contribution to journalArticle

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