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Open Access Amelioration of Paraquat-Induced Pulmonary Injury by Mesenchymal Stem Cells

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Acute paraquat (PQ) poisoning induces redox cycle and leads to fatal injury of lung. Clinical management is supportive in nature due to lack of effective antidote, and the mortality is very high. Mesenchymal stem cells (MSCs) process the properties of immunomodulation, anti-inflammatory, and antifibrotic effects and oxidative stress resistance. MSC transplantation may theoretically serve as an antidote in PQ intoxication. In this study, we examined the potential therapeutic effects of MSCs in PQ-induced lung injury. The degree of PQ toxicity in the rat type II pneumocyte cell line, L2, and MSCs was evaluated by examining cell viability, ultrastructural changes, and gene expression. L2 cells treated with 0.5 mM PQ were cocultured in the absence or presence of MSCs. For the in vivo study, adult male SD rats were administered an intraperitoneal injection of PQ (24 mg/kg body weight) and were divided into three groups: group I, control; group II, cyclophosphamide and methylprednisolone; group III, MSC transplantation 6 h after PQ exposure. MSCs were relatively resistant to PQ toxicity. Coculture with MSCs significantly inhibited PQ accumulation in L2 cells and upregulated the expression of antioxidative heme oxygenase 1 and metallothionein 1a genes, reversed epithelial-to-mesenchymal transition, and increased the viability of PQ-exposed L2 cells. Treatment with MSCs resulted in a significant reduction in severity of liver and renal function deterioration, alleviated lung injury, and prolonged the life span of rats. Altogether, our results suggest that MSCs possess antidote-like effect through multifactorial protection mechanism. The results of this preclinical study demonstrate that transplantation of MSCs may be a promising therapy and should be further validated clinically.
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Keywords: Mesenchymal stem cells (MSCs); Oxidative stress; Paraquat (PQ); Pulmonary injury

Document Type: Research Article

Affiliations: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan

Publication date: 2013-09-11

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  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.

    Cell Transplantation is now being published by SAGE. Please visit their website for the most recent issues.

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