Gene delivery by the hSP-B promoter to lung alveolar type II epithelial cells in LAL-knockout mice through bone marrow mesenchymal stem cells.
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.
Yan
C
C
The Center for Immunobiology, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. coyan@iupui.edu
Lian
X
X
Dai
Y
Y
Wang
X
X
Qu
P
P
White
A
A
Qin
Y
Y
Du
H
H
D000818:Animals; D001854:Bone Marrow Cells / Q000201:enzymology; D004847:Epithelial Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D007763:Lac Operon; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023421:Models, Animal; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics*; D011510:Proteolipids / Q000235:genetics*; D011650:Pulmonary Alveoli; D002787:Sterol Esterase / Q000172:deficiency / Q000235:genetics*
D011498:Protein Precursors; D011510:Proteolipids; C105511:surfactant protein B propeptide; D002787:Sterol Esterase