Human Amnion-Derived MSCs Alleviate Acute Lung Injury and Hinder Pulmonary Fibrosis Caused by Paraquat in Rats

Background/Aims. Paraquat is an effective herbicide used worldwide. Due to high lung toxicity and a lack of effective treatment, elevated morbidity and mortality occur after ingestion. Mesenchymal stem cells (MSCs) may be an option for repairing, remodeling, or regenerating lungs damaged by paraquat. Human amnion-derived mesenchymal stem cells (hAD-MSCs) have significant biological advantages including low immunogenicity and noninvasive acquisition for acute and chronic lung injury. In this study, the preclinical efficacy of hAD-MSCs in treating paraquat-induced acute lung injury and pulmonary fibrosis was investigated. Clinical cell therapy was replicated including the dose and timing of hAD-MSC treatment. Methods. First, the purity of hAD-MSCs was determined by morphological observation and FCM, and the effects on the survival of paraquat-poisoned Sprague-Dawley rats were observed. All rats were randomly divided into three groups, defined as the sham control group ( n = 8 ), model group ( n = 15 ), and hAD-MSC-transplanted group ( n = 17 ). Pneumonocyte damage and inflammatory cell infiltration were investigated in the three groups of rats, untreated control, paraquat only, and paraquat+hAD-MSC transplanted, using H&E staining. Fibrosis was investigated in three groups of rats using Masson’s trichrome staining and Sirius red staining. The profibrotic factor TGF-β1, the composition of fibrotic collagen HYP, and the hAD-MSC-secreted immunosuppressive factor HLA-G5 in serum were investigated in the three groups of rats using ELISA. Furthermore, the distribution of hAD-MSCs was investigated in the three groups of rats using immunohistochemistry and hematoxylin staining. Results. The hAD-MSCs exhibited typical hallmarks of MSCs, improved the state of being and survival of paraquat-poisoned rats, reduced both lung injury and inflammation, and inhibited the progression of pulmonary fibrosis by decreasing the deposition of collagen and the secretion of both TGF-β1 and HYP. The hAD-MSCs could survive in damaged lungs and secreted appropriate amounts of HLA-G5 into the serum. Conclusion. The obtained results indicate that hAD-MSCs used to treat paraquat-induced lung injury may work through anti-inflammatory and immunosuppressive pathways and the downregulation of profibrotic elements. This study suggests that the transplantation of hAD-MSCs is a promising therapeutic approach for the treatment of paraquat-intoxicated patients.