Now at the Institute of Respiratory Medicine, Pulmonary Hospital, Tongji University, Shanghai, People's Republic of China.
Mesenchymal stem cell-based angiopoietin-1 gene therapy for acute lung injury induced by lipopolysaccharide in mice†
Article first published online: 11 DEC 2007
Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 214, Issue 4, pages 472–481, March 2008
How to Cite
Xu, J., Qu, J., Cao, L., Sai, Y., Chen, C., He, L. and Yu, L. (2008), Mesenchymal stem cell-based angiopoietin-1 gene therapy for acute lung injury induced by lipopolysaccharide in mice. J. Pathol., 214: 472–481. doi: 10.1002/path.2302
No conflicts of interest were declared.
- Issue published online: 8 FEB 2008
- Article first published online: 11 DEC 2007
- Accepted manuscript online: 11 DEC 2007 12:00AM EST
- Manuscript Accepted: 11 NOV 2007
- Manuscript Revised: 20 OCT 2007
- Manuscript Received: 9 MAY 2007
- Specialized Research Fund for the Doctoral Programme of China. Grant Number: 20050246047
- Key Project of Science and Technology Commission of Shanghai Municipality, People's Republic of China. Grant Number: 05JC14015
- mesenchymal stem cells;
- lung injury;
- gene therapy
Bone marrow-derived mesenchymal stem cells (MSCs) can serve as a vehicle for gene therapy. Angiopoietin-1 (Ang1) is a critical factor for endothelial survival and vascular stabilization via the inhibition of endothelial permeability and leukocyte–endothelium interactions. We hypothesized that MSC-based Ang1 gene therapy might be a potential therapeutic approach for lipopolysaccharide (LPS)-induced lung injury. MSCs were isolated from 6 week-old inbred male mice and transduced with the Ang1 gene, using a lentivirus vector. The MSCs showed no significant phenotypic changes after transduction. In the in vivo mouse model, the LPS-induced lung injury was markedly alleviated in the group treated with MSCs carrying Ang1 (MSCs–Ang1), compared with groups treated with MSCs or Ang1 alone. The expression of Ang1 protein in the recipient lungs was increased after MSCs–Ang1 administration. The histopathological and biochemical indices of LPS-induced lung injury were improved after MSCs-based Ang1 gene treatment. MSCs–Ang1 administration also reduced pulmonary vascular endothelial permeability and the recruitment of inflammatory cells into the lung. Cells of MSC origin could be detected in the recipient lungs for 2 weeks after injection with MSCs. These results suggest that MSCs and Ang1 have a synergistic role in the treatment of LPS-induced lung injury. MSC-based Ang1 gene therapy may be developed as a potential novel strategy for the treatment of acute lung injury. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.