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. 2007 Oct;14(20):1461-70. doi: 10.1038/sj.gt.3303006. Epub 2007 Aug 16.

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 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone Marrow Cells / enzymology
  • Epithelial Cells / enzymology
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Expression
  • Genetic Therapy / methods*
  • Lac Operon
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / enzymology
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Animal
  • Pneumonia / immunology
  • Pneumonia / metabolism
  • Pneumonia / therapy*
  • Promoter Regions, Genetic*
  • Protein Precursors / genetics*
  • Proteolipids / genetics*
  • Pulmonary Alveoli
  • Sterol Esterase / deficiency
  • Sterol Esterase / genetics*

Substances

  • Protein Precursors
  • Proteolipids
  • surfactant protein B propeptide
  • Sterol Esterase