Mesenchymal stem cell therapy for paraquat poisoning: A systematic review and meta-analysis of preclinical studies

Abstract

BackgroundParaquat (PQ) poisoning can cause multiple organ failure, in which the lung is the primary target organ. There is currently no treatment for PQ poisoning. Mesenchymal stem cells (MSCs), which differentiate into multiple cell types, have generated much enthusiasm regarding their use for the treatment of several diseases. The aim of this study was to systematically review and analyze published preclinical studies describing MSC administration for the treatment of PQ poisoning in animal models to provide a basis for cell therapy.MethodsThe electronic databases PubMed and CBMdisc were searched in this systematic review and meta-analysis. The MSC treatment characteristics of animal models of PQ poisoning were summarized. After quality assessment was performed, the effects of MSC transplantation were evaluated based on the survival rate, lung wet/dry weight, fibrosis scores, oxidative stress response, and inflammatory response. Publication bias was assessed.ResultsEleven controlled preclinical studies involving MSC transplantation in animal models of PQ poisoning were included in this review. MSC therapy improved the survival rate and reduced the lung wet/dry weight and histopathological fibrosis changes in most studies. MSCs decreased serum or plasma malondialdehyde levels in the acute phase after 7 and 14 d and increased serum or plasma superoxide dismutase and glutathione levels at the same time points. IL-1β, TNF-α and TGF-β1 levels in blood or lung tissues were decreased to different degrees by MSCs. Lung hydroxyproline was decreased by MSCs after 14 d. No obvious evidence of publication bias was found.ConclusionMSCs showed anti-fibrosis therapeutic effects in animal models of lung injury caused by PQ poisoning, which may be related to reduced oxidative stress and inflammatory cytokine levels. Our review indicates a potential therapeutic role for MSC therapy to treat PQ poisoning and serves to augment the rationale for clinical studies.

Mesenchymal Stromal Cells Anno 2019: Dawn of the Therapeutic Era? Concise Review

“…In parallel to these changes of paradigm regarding the mechanism of action of MSC treatment over the last decade, numerous preclinical studies testing MSCs in a great variety of experimental animal models of immune‐mediated diseases have been carried out, showing in most cases good safety and efficacy results . These encouraging results prompted researchers to test the feasibility, safety, and efficacy of MSCs treatment in human clinical trials in a variety of indications (920 at the start of 2019 according to).…”

Ginsenoside Rg1 as an Effective Regulator of Mesenchymal Stem Cells

“…Meanwhile, these cells exhibit a fibroblastic morphology, adhere to a plastic surface when cultured in vitro, and share a common immunophenotype consisting of positive CD105, CD73, and CD90 expression and negative CD45, CD34, CD14, CD19, and HLA-DR expression (Wagers and Weissman, 2004). MSCs showing low immunogenicity are used for xenotransplantation to achieve immunomodulation and improve tissue regeneration (Jiang et al, 2002;He et al, 2018b). Thus, these cells are considered promising candidates in the management of several conditions, such as bone regeneration (Bruder et al, 1998), certain neurodegenerative disorders (Crigler et al, 2006), and graft-versus-host disease (Le Blanc et al, 2004).…”

Combined Signaling of NF-kappaB and IL-17 Contributes to Mesenchymal Stem Cells-Mediated Protection for Paraquat-induced Acute Lung Injury

“…MSCs can be derived from many sources, such as bone marrow, umbilical cord blood, dental pulp, adipose tissue and adult organs (Augustine et al, 2017;He et al, 2018). These cells can be isolated via adherence to a plastic surface and share a common immuno-phenotype with CD105, CD73 and CD90 expression, but without CD45, CD34, CD14, CD19 and HLADR expression (Augustine et al, 2017).…”

“…These cells can be isolated via adherence to a plastic surface and share a common immuno-phenotype with CD105, CD73 and CD90 expression, but without CD45, CD34, CD14, CD19 and HLADR expression (Augustine et al, 2017). MSCs with low immunogenicity are used for xenogenous transplantation to achieve immunomodulation and improve tissue repair (He et al, 2018) (Augustine et al, 2017). Thus, MSC transplantation has also been a potential therapeutic approach for ALI induced by PQ poisoning (Dorooshi et al, 2018).…”

“…Thus, MSC transplantation has also been a potential therapeutic approach for ALI induced by PQ poisoning (Dorooshi et al, 2018). MSC transplantation was showed to increase the survival time, decease the ratio of lung wet/dry weight and reduce the levels of inflammation and ROS production in rats upon PQ treatment (He et al, 2018). Although MSC transplantation has been explored in a variety of pulmonary disease models, the molecular mechanisms that are beneficial for PQ-induced ALI have yet to be understood (Yang et al, 2011).…”