title: Therapeutic Effects of Bone Marrow-Derived Mesenchymal Stem Cells in Models of Pulmonary and Extrapulmonary Acute Lung Injury.
abstract: Bone marrow-derived mesenchymal stem cells (MSCs) offer a promising therapy for acute lung injury (ALI). However, whether the same MSC treatments possess similar potential for different ALI models is not fully clear. The present study evaluated the distribution and therapeutic effects of intravenous MSC administration for the treatment of intratracheal lipopolysaccharide (LPS)-induced intrapulmonary ALI and intravenous LPS/zymosan-induced extrapulmonary ALI, matched with lung injury severity, at 30 min and 1, 3, and 7 days. We found that MSC transplantation attenuated lung injury and inhibited lung inflammation in both ALI models. The benefits of MSCs were more significant in the intrapulmonary ALI mice. In vivo and ex vivo fluorescence imaging showed that MSCs primarily homed into the lung. However, more MSCs were recruited into the lungs of the intrapulmonary ALI mice than those of the extrapulmonary ALI mice over the time course. A few MSCs were also detected in the liver and spleen at days 3 and 7. In addition, the two ALI models showed different extrapulmonary organ dysfunction. A lower percentage of cell apoptosis and SDF-1α levels was found in the liver and spleen of the intrapulmonary ALI mice than in those of the extrapulmonary ALI mice. These results suggested that the two ALI models were accompanied with different degrees of extrapulmonary organ damage, which resulted in differences in the trafficking and accumulation of MSCs to the injured lung and consequently accounted for different therapeutic effects of MSCs for lung repair in the two ALI models. These data suggest that intravenous administration of MSCs has a greater potential for the treatment of intrapulmonary ALI than extrapulmonary ALI matched with lung injury severity; these differences were due to more recruitment of MSCs in the lungs of intrapulmonary ALI mice than those of extrapulmonary ALI mice. This finding may contribute to the clinical use of MSCs for the treatment of ALI.
authors.affiliation: Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, P. R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Hongli
authors.initials: H
authors.lastname: He
authors.forename: Airan
authors.initials: A
authors.lastname: Liu
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Xu
authors.forename: Jibin
authors.initials: J
authors.lastname: Han
authors.forename: Qihong
authors.initials: Q
authors.lastname: Chen
authors.forename: Shuling
authors.initials: S
authors.lastname: Hu
authors.forename: Xiuping
authors.initials: X
authors.lastname: Xu
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Huang
authors.forename: Fengmei
authors.initials: F
authors.lastname: Guo
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Haibo
authors.initials: H
authors.lastname: Qiu
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000628:therapy*; D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology*; D002460:Cell Line; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D054377:Chemokine CXCL12 / Q000378:metabolism; D004195:Disease Models, Animal; D057809:HEK293 Cells; D006801:Humans; D008070:Lipopolysaccharides; D008099:Liver / Q000166:cytology; D008168:Lung / Q000166:cytology / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000628:therapy*; D013154:Spleen / Q000166:cytology; D015054:Zymosan
chemical_list: D054377:Chemokine CXCL12; D008070:Lipopolysaccharides; D015054:Zymosan