Human amniotic mesenchymal stem cells alleviate paraquat-induced pulmonary fibrosis in rats by inhibiting the inflammatory response

Life Sci. 2020 Feb 15:243:117290. doi: 10.1016/j.lfs.2020.117290. Epub 2020 Jan 8.

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.

Keywords: CD3+ T cell; Histopathology; Human amniotic mesenchymal stem cells; Inflammatory factor; Lactic acid; Paraquat poisoning; Pulmonary fibrosis; human anti-nuclei antibody MAB1281.

MeSH terms

  • Amniotic Fluid / cytology*
  • Animals
  • Female
  • Herbicides / toxicity*
  • Humans
  • Inflammation / prevention & control*
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Paraquat / toxicity*
  • Pulmonary Fibrosis / chemically induced*
  • Pulmonary Fibrosis / prevention & control*
  • Rats
  • Rats, Sprague-Dawley
  • Survival Rate

Substances

  • Herbicides
  • Paraquat