Mesenchymal stem cell-based developmental endothelial locus-1 gene therapy for acute lung injury induced by lipopolysaccharide in mice

Zhao,Yun-Feng; Xiong,Wei; Wu,Xue-Ling

doi:10.3892/mmr.2014.1988

May-2014 Volume 9 Issue 5

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

May-2014 Volume 9 Issue 5

Full Size Image

Article

Mesenchymal stem cell-based developmental endothelial locus-1 gene therapy for acute lung injury induced by lipopolysaccharide in mice

Authors:
- Yun-Feng Zhao
- Wei Xiong
- Xue-Ling Wu
View Affiliations / Copyright

Affiliations: Department of Respiratory Medicine, Pudong New Area, Gongli Hospital, Shanghai 200135, P.R. China, Institute of Respiratory Medicine, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China
Pages: 1583-1589
|
Published online on: February 26, 2014

https://doi.org/10.3892/mmr.2014.1988
Expand metrics +

Abstract

Studies have suggested that bone marrow-derived mesenchymal stem cells (MSCs) may be used as a tool for gene therapy. Developmental endothelial locus-1 (Del-1) is a critical factor for cell migration and infiltration via the inhibition of the function of a major leukocyte adhesion receptor LFA-1 which prevents leukocyte adhesion to the endothelium. In the present study, we hypothesized that MSC-based Del-1 gene therapy may have potential therapeutic applications for lipopolysaccharide (LPS)-induced lung injury. The MSCs in the present assay were isolated from 6 week-old male mice. In order to investigate the therapeutic effect of the Del-1 gene on LPS-induced ALI mice, a lentivirus vector containing the Del-1 gene was constructed and transduced into the MSCs. In the in vivo assay, we induced lung injury with LPS injection and treated mice with different groups of MSCs, and compared with groups treated with MSCs alone, we observed that the administration with MSCs carrying Del-1 (MSCs-Del1) markedly alleviated the LPS-induced lung injury. There were significant decreases in the number of neutrophils in bronchoalveolar lavage (BAL) and the serum levels of TNF-α and IL-6 in the Del-1-expressed MSC‑treated mice. Furthermore, compared with MSCs treated alone, Del1-MSC‑treated mice also exhibited low lung injury scores, high protein concentrations and myeloperoxidase activity. In conclusion, treatment with Del-1-expressed MSCs significantly decreases the severity of endotoxin-induced acute lung injury and the level of inflammatory cytokines in mice.

View Figures

View References

1	Rubenfeld GD, Caldwell E, Peabody E, Weaver J, et al: Incidence and outcomes of acute lung injury. N Engl J Med. 353:1685–1693. 2005. View Article : Google Scholar : PubMed/NCBI
2	Sheu CC, Gong MN, Zhai R, et al: Clinical characteristics and outcomes of sepsis-related vs non-sepsis-related ARDS. Chest. 138:559–567. 2010. View Article : Google Scholar : PubMed/NCBI
3	Hu X, Qian S, Xu F, et al: Incidence, management and mortality of acute hypoxemic respiratory failure and acute respiratory distress syndrome from a prospective study of Chinese paediatric intensive care network. Acta Paediatr. 99:715–721. 2010.
4	Ware LB, Koyama T, Billheimer DD, et al: Prognostic and pathogenetic value of combining clinical and biochemical indices in patients with acute lung injury. Chest. 137:288–296. 2010. View Article : Google Scholar : PubMed/NCBI
5	Cribbs SK, Matthay MA and Martin GS: Stem cells in sepsis and acute lung injury. Crit Care Med. 38:2379–2385. 2010. View Article : Google Scholar : PubMed/NCBI
6	Lee JW, Gupta N, Serikov V and Matthay MA: Potential application of mesenchymal stem cells in acute lung injury. Expert Opin Biol Ther. 9:1259–1270. 2009. View Article : Google Scholar : PubMed/NCBI
7	Matthay MA, Goolaerts A, Howard JP and Lee JW: Mesenchymal stem cells for acute lung injury: preclinical evidence. Crit Care Med. 38(Suppl): S569–S573. 2010. View Article : Google Scholar : PubMed/NCBI
8	Das R, Jahr H, van Osch GJ and Farrell E: The role of hypoxia in bone marrow-derived mesenchymal stem cells: considerations for regenerative medicine approaches. Tissue Eng Part B Rev. 16:159–168. 2010. View Article : Google Scholar : PubMed/NCBI
9	Rojas M, Xu J, Woods CR, et al: Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol. 33:145–152. 2005. View Article : Google Scholar : PubMed/NCBI
10	Krause DS, Theise ND, Collector MI, et al: Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell. 105:369–377. 2001. View Article : Google Scholar : PubMed/NCBI
11	Krause DS: Bone marrow-derived cells and stem cells in lung repair. Proc Am Thorac Soc. 5:323–327. 2008. View Article : Google Scholar : PubMed/NCBI
12	Gupta N, Su X, Popov B, Lee JW, Serikov V and Matthay MA: Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol. 179:1855–1863. 2007. View Article : Google Scholar : PubMed/NCBI
13	Xu J, Woods CR, Mora AL, et al: Prevention of endotoxin-induced systemic response by bone marrow-derived mesenchymal stem cells in mice. Am J Physiol Lung Cell Mol Physiol. 293:L131–L141. 2007. View Article : Google Scholar : PubMed/NCBI
14	Xu J, Qu J, Cao L, et al: Mesenchymal stem cell-based angiopoietin-1 gene therapy for acute lung injury induced by lipopolysaccharide in mice. J Pathol. 214:472–481. 2008. View Article : Google Scholar : PubMed/NCBI
15	Phillipson M, Heit B, Colarusso P, Liu L, Ballantyne CM and Kubes P: Intraluminal crawling of neutrophils to emigration sites: a molecularly distinct process from adhesion in the recruitment cascade. J Exp Med. 203:2569–2575. 2006. View Article : Google Scholar : PubMed/NCBI
16	Schenkel AR, Mamdouh Z and Muller WA: Locomotion of monocytes on endothelium is a critical step during extravasation. Nat Immunol. 5:393–400. 2004. View Article : Google Scholar : PubMed/NCBI
17	Barreiro O, Yanez-Mo M, Serrador JM, et al: Dynamic interaction of VCAM-1 and ICAM-1 with moesin and ezrin in a novel endothelial docking structure for adherent leukocytes. J Cell Biol. 157:1233–1245. 2002. View Article : Google Scholar : PubMed/NCBI
18	Choi EY, Chavakis E, Czabanka MA, et al: Del-1, an endogenous leukocyte-endothelial adhesion inhibitor, limits inflammatory cell recruitment. Science. 322:1101–1104. 2008. View Article : Google Scholar : PubMed/NCBI
19	Gray KD, Simovic MO, Chapman WC, et al: Endotoxin potentiates lung injury in cerulein-induced pancreatitis. Am J Surg. 186:526–530. 2003. View Article : Google Scholar : PubMed/NCBI
20	Aslam M, Baveja R, Liang OD, et al: Bone marrow stromal cells attenuate lung injury in a murine model of neonatal chronic lung disease. Am J Respir Crit Care Med. 180:1122–1130. 2009. View Article : Google Scholar : PubMed/NCBI
21	Ortiz LA, Gambelli F, McBride C, et al: Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci USA. 100:8407–8411. 2003. View Article : Google Scholar : PubMed/NCBI
22	van Haaften T, Byrne R, Bonnet S, et al: Airway delivery of mesenchymal stem cells prevents arrested alveolar growth in neonatal lung injury in rats. Am J Respir Crit Care Med. 180:1131–1142. 2009.PubMed/NCBI
23	Basit A, Reutershan J, Morris MA, Solga M, Rose CE Jr and Ley K: ICAM-1 and LFA-1 play critical roles in LPS-induced neutrophil recruitment into the alveolar space. Am J Physiol Lung Cell Mol Physiol. 291:L200–L207. 2006. View Article : Google Scholar : PubMed/NCBI
24	Choi EY: Inhibition of leukocyte adhesion by developmental endothelial locus-1 (del-1). Immune Netw. 9:153–157. 2009. View Article : Google Scholar : PubMed/NCBI