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

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.