Intrapleural delivery of MSCs attenuates acute lung injury by paracrine/endocrine mechanism

Journal of Cellular and Molecular Medicine

Zhao-hui Qin¹  Jin-fu Xu⁵  Jie-ming Qu¹  Jing Zhang²  Yin Sai⁴  Chun-mei Chen⁴  Lian Wu³ 

[1] Department of Pulmonary Medicine, Huadong Hospital, Shanghai Medical College, Fudan University, Shanghai, China;Department of Pulmonary Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China;Department of Pharmacology & Clinical Pharmacology, University of Auckland, New Zealand;State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China;Department of Pulmonary Medicine, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China

关键词: mesenchymal stem cells;    acute lung injury;    pleural cavity;    lipopolysaccharides;    cell therapy;   

DOI  :  10.1111/j.1582-4934.2012.01597.x

来源: Wiley

【 摘 要 】

Abstract

Two different repair mechanisms of mesenchymal stem cells (MSCs) are suggested to participate in the repair of acute lung injury (ALI): (i) Cell engraftment mechanism, (ii) Paracrine/endocrine mechanism. However, the exact roles they play in the repair remain unclear. The aim of the study was to evaluate the role of paracrine/endocrine mechanism using a novel intrapleural delivery method of MSCs. Either 1 × 10⁶ MSCs in 300 μl of PBS or 300 μl PBS alone were intrapleurally injected into rats with endotoxin-induced ALI. On days 1, 3 or 7 after injections, samples of lung tissues and bronchoalveolar lavage fluid (BALF) were collected from each rat for assessment of lung injury, biochemical analysis and histology. The distribution of MSCs was also traced by labelling the cells with 4′,6-diamidino-2-phenylindole dihydrochloride (DAPI). MSCs intrapleural injection significantly improved LPS-induced lung histopathology compared with PBS-treated group at day 3. There was also a significant decrease in total cell counts and protein concentration in BALF at day 7 in the MSCs -treated rats compared to PBS control group. Tracking the DAPI-marked MSCs showed that there were no exotic MSCs in the lung parenchyma. MSCs administration resulted in a down-regulation of pro-inflammatory response to endotoxin by reducing TNF-α both in the BALF and in the lung, while up-regulating the anti-inflammatory cytokine IL-10 in the lung. In conclusion, treatment with intrapleural MSCs administration markedly attenuates the severity of endotoxin-induced ALI. This role is mediated by paracrine/endocrine repair mechanism of MSCs rather than by the cell engraftment mechanism.

【 授权许可】

Unknown   
© 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd