Fang He1, Yuying Wang2, Yuxiang Li3, Limei Yu4. 1. Key Laboratory of Cell Engineering in Guizhou Province, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, PR China; Biological Treatment Talent Base of Guizhou Province, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, PR China; Zunyi Stem Cell and Regenerative Medicine Engineering Research Center, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, PR China. Electronic address: hfwyyx@yeah.net. 2. Key Laboratory of Cell Engineering in Guizhou Province, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, PR China; Biological Treatment Talent Base of Guizhou Province, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, PR China; Zunyi Stem Cell and Regenerative Medicine Engineering Research Center, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, PR China. Electronic address: wangyuyingangle@163.com. 3. Key Laboratory of Cell Engineering in Guizhou Province, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, PR China; Biological Treatment Talent Base of Guizhou Province, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, PR China; Zunyi Stem Cell and Regenerative Medicine Engineering Research Center, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, PR China. Electronic address: 814326940@qq.com. 4. Key Laboratory of Cell Engineering in Guizhou Province, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, PR China; Biological Treatment Talent Base of Guizhou Province, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, PR China; Zunyi Stem Cell and Regenerative Medicine Engineering Research Center, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, PR China. Electronic address: ylm720@yeah.net.
Abstract
AIMS: To investigate the therapeutic effects of human amniotic mesenchymal stem cells (hAMSCs) on paraquat (PQ)-induced pulmonary fibrosis in rats and investigate the inflammatory mechanisms. MAIN METHODS: hAMSCs were identified by morphological, flow cytometry and immunocytochemistry. A pulmonary fibrosis model was induced by administering PQ to rats. The hAMSCs group was treated with hAMSCs after 6 h of PQ poisoning. At 21 days after hAMSCs transplantation, lungs were harvested for H&E, Masson and immunohistochemical staining to evaluate pulmonary histopathology, collagen deposition, CD3+ cell infiltration and hAMSCs colonization. Arterial blood was used for lactic acid analysis and venous blood was used to detect TNF-α, IL-6, and TGF-β1 by ELISA method. KEY FINDINGS: hAMSCs can improve the lung structure and decrease collagen deposition induced by PQ. The membranes of CD3+ T cell in the PQ group were round and complete, while that in the hAMSCs group rats exhibited punctate or diffuse staining. In addition, the CD3+ cell was decreased by hAMSCs administration, and MAB1281-positive cells were detected in lung of hAMSCs group rats. The survival rate of the hAMSCs group was significantly higher than that of the PQ group at 21 days after injection. TNF-α, IL-6, TGF-β1 and lactic acid were significantly decreased by hAMSCs administration. SIGNIFICANCE: hAMSCs have a significant therapeutic effect on pulmonary fibrosis induced by acute PQ poisoning and can improve survival rate in rats. Furthermore, hAMSCs administration can improve lung histopathology and reduce collagen deposition by reducing inflammatory CD3+ T cell infiltration, inflammatory cytokine expression and lactic acid levels.
AIMS: To investigate the therapeutic effects of human amniotic mesenchymal stem cells (hAMSCs) on paraquat (PQ)-induced pulmonary fibrosis in rats and investigate the inflammatory mechanisms. MAIN METHODS: hAMSCs were identified by morphological, flow cytometry and immunocytochemistry. A pulmonary fibrosis model was induced by administering PQ to rats. The hAMSCs group was treated with hAMSCs after 6 h of PQ poisoning. At 21 days after hAMSCs transplantation, lungs were harvested for H&E, Masson and immunohistochemical staining to evaluate pulmonary histopathology, collagen deposition, CD3+ cell infiltration and hAMSCs colonization. Arterial blood was used for lactic acid analysis and venous blood was used to detect TNF-α, IL-6, and TGF-β1 by ELISA method. KEY FINDINGS: hAMSCs can improve the lung structure and decrease collagen deposition induced by PQ. The membranes of CD3+ T cell in the PQ group were round and complete, while that in the hAMSCs group rats exhibited punctate or diffuse staining. In addition, the CD3+ cell was decreased by hAMSCs administration, and MAB1281-positive cells were detected in lung of hAMSCs group rats. The survival rate of the hAMSCs group was significantly higher than that of the PQ group at 21 days after injection. TNF-α, IL-6, TGF-β1 and lactic acid were significantly decreased by hAMSCs administration. SIGNIFICANCE: hAMSCs have a significant therapeutic effect on pulmonary fibrosis induced by acute PQ poisoning and can improve survival rate in rats. Furthermore, hAMSCs administration can improve lung histopathology and reduce collagen deposition by reducing inflammatory CD3+ T cell infiltration, inflammatory cytokine expression and lactic acid levels.