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Mesenchymal stem cells transfected with sFgl2 inhibit the acute rejection of heart transplantation in mice by regulating macrophage activation

BACKGROUND: Mesenchymal stem cells (MSCs) have become a promising candidate for cell-based immune therapy for acute rejection (AR) after heart transplantation due to possessing immunomodulatory properties. In this study, we evaluated the efficacy of soluble fibronectin-like protein 2 (sFgl2) overexp...

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Autores principales: Gao, Chao, Wang, Xiaodong, Lu, Jian, Li, Zhilin, Jia, Haowen, Chen, Minghao, Chang, Yuchen, Liu, Yanhong, Li, Peiyuan, Zhang, Baotong, Du, Xuezhi, Qi, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301524/
https://www.ncbi.nlm.nih.gov/pubmed/32552823
http://dx.doi.org/10.1186/s13287-020-01752-1
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author Gao, Chao
Wang, Xiaodong
Lu, Jian
Li, Zhilin
Jia, Haowen
Chen, Minghao
Chang, Yuchen
Liu, Yanhong
Li, Peiyuan
Zhang, Baotong
Du, Xuezhi
Qi, Feng
author_facet Gao, Chao
Wang, Xiaodong
Lu, Jian
Li, Zhilin
Jia, Haowen
Chen, Minghao
Chang, Yuchen
Liu, Yanhong
Li, Peiyuan
Zhang, Baotong
Du, Xuezhi
Qi, Feng
author_sort Gao, Chao
collection PubMed
description BACKGROUND: Mesenchymal stem cells (MSCs) have become a promising candidate for cell-based immune therapy for acute rejection (AR) after heart transplantation due to possessing immunomodulatory properties. In this study, we evaluated the efficacy of soluble fibronectin-like protein 2 (sFgl2) overexpressing mesenchymal stem cells (sFgl2-MSCs) in inhibiting AR of heart transplantation in mice by regulating immune tolerance through inducing M2 phenotype macrophage polarization. METHODS AND RESULTS: The sFgl2, a novel immunomodulatory factor secreted by regulatory T cells, was transfected into MSCs to enhance their immunosuppressive functions. After being co-cultured for 72 h, the sFgl2-MSCs inhibited M1 polarization whereas promoted M2 of polarization macrophages through STAT1 and NF-κB pathways in vitro. Besides, the sFgl2-MSCs significantly enhanced the migration and phagocytosis ability of macrophages stimulated with interferon-γ (IFN-γ) and lipopolysaccharide (LPS). Further, the application potential of sFgl2-MSCs in AR treatment was demonstrated by heterotopic cardiac transplantation in mice. The tissue damage and macrophage infiltration were evaluated by H&E and immunohistochemistry staining, and the secretion of inflammatory cytokines was analyzed by ELISA. The results showed that sFgl2-MSCs injected intravenously were able to locate in the graft, promote the M2 polarization of macrophages in vivo, regulate the local and systemic immune response, significantly protect tissues from damaging, and finally prolonged the survival time of mice heart grafts. CONCLUSION: sFgl2-MSCs ameliorate AR of heart transplantation by regulating macrophages, which provides a new idea for the development of anti-AR treatment methods after heart transplantation.
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spelling pubmed-73015242020-06-18 Mesenchymal stem cells transfected with sFgl2 inhibit the acute rejection of heart transplantation in mice by regulating macrophage activation Gao, Chao Wang, Xiaodong Lu, Jian Li, Zhilin Jia, Haowen Chen, Minghao Chang, Yuchen Liu, Yanhong Li, Peiyuan Zhang, Baotong Du, Xuezhi Qi, Feng Stem Cell Res Ther Research BACKGROUND: Mesenchymal stem cells (MSCs) have become a promising candidate for cell-based immune therapy for acute rejection (AR) after heart transplantation due to possessing immunomodulatory properties. In this study, we evaluated the efficacy of soluble fibronectin-like protein 2 (sFgl2) overexpressing mesenchymal stem cells (sFgl2-MSCs) in inhibiting AR of heart transplantation in mice by regulating immune tolerance through inducing M2 phenotype macrophage polarization. METHODS AND RESULTS: The sFgl2, a novel immunomodulatory factor secreted by regulatory T cells, was transfected into MSCs to enhance their immunosuppressive functions. After being co-cultured for 72 h, the sFgl2-MSCs inhibited M1 polarization whereas promoted M2 of polarization macrophages through STAT1 and NF-κB pathways in vitro. Besides, the sFgl2-MSCs significantly enhanced the migration and phagocytosis ability of macrophages stimulated with interferon-γ (IFN-γ) and lipopolysaccharide (LPS). Further, the application potential of sFgl2-MSCs in AR treatment was demonstrated by heterotopic cardiac transplantation in mice. The tissue damage and macrophage infiltration were evaluated by H&E and immunohistochemistry staining, and the secretion of inflammatory cytokines was analyzed by ELISA. The results showed that sFgl2-MSCs injected intravenously were able to locate in the graft, promote the M2 polarization of macrophages in vivo, regulate the local and systemic immune response, significantly protect tissues from damaging, and finally prolonged the survival time of mice heart grafts. CONCLUSION: sFgl2-MSCs ameliorate AR of heart transplantation by regulating macrophages, which provides a new idea for the development of anti-AR treatment methods after heart transplantation. BioMed Central 2020-06-17 /pmc/articles/PMC7301524/ /pubmed/32552823 http://dx.doi.org/10.1186/s13287-020-01752-1 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Gao, Chao
Wang, Xiaodong
Lu, Jian
Li, Zhilin
Jia, Haowen
Chen, Minghao
Chang, Yuchen
Liu, Yanhong
Li, Peiyuan
Zhang, Baotong
Du, Xuezhi
Qi, Feng
Mesenchymal stem cells transfected with sFgl2 inhibit the acute rejection of heart transplantation in mice by regulating macrophage activation
title Mesenchymal stem cells transfected with sFgl2 inhibit the acute rejection of heart transplantation in mice by regulating macrophage activation
title_full Mesenchymal stem cells transfected with sFgl2 inhibit the acute rejection of heart transplantation in mice by regulating macrophage activation
title_fullStr Mesenchymal stem cells transfected with sFgl2 inhibit the acute rejection of heart transplantation in mice by regulating macrophage activation
title_full_unstemmed Mesenchymal stem cells transfected with sFgl2 inhibit the acute rejection of heart transplantation in mice by regulating macrophage activation
title_short Mesenchymal stem cells transfected with sFgl2 inhibit the acute rejection of heart transplantation in mice by regulating macrophage activation
title_sort mesenchymal stem cells transfected with sfgl2 inhibit the acute rejection of heart transplantation in mice by regulating macrophage activation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301524/
https://www.ncbi.nlm.nih.gov/pubmed/32552823
http://dx.doi.org/10.1186/s13287-020-01752-1
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