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IGF-1C hydrogel improves the therapeutic effects of MSCs on colitis in mice through PGE(2)-mediated M2 macrophage polarization
Background: Mesenchymal stem cell (MSC)-based therapies hold great promise for the treatment of inflammatory bowel disease (IBD). In order to optimize and maximize the therapeutic benefits of MSCs, we investigated whether cotransplantation of a chitosan (CS)-based injectable hydrogel with immobilize...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359093/ https://www.ncbi.nlm.nih.gov/pubmed/32685014 http://dx.doi.org/10.7150/thno.45434 |
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author | Cao, Xiaocang Duan, Liyun Hou, Huixing Liu, Yue Chen, Shang Zhang, Shuaiqiang Liu, Yuanyuan Wang, Chen Qi, Xin Liu, Na Han, Zhibo Zhang, Dekui Han, Zhong-Chao Guo, Zhikun Zhao, Qiang Li, Zongjin |
author_facet | Cao, Xiaocang Duan, Liyun Hou, Huixing Liu, Yue Chen, Shang Zhang, Shuaiqiang Liu, Yuanyuan Wang, Chen Qi, Xin Liu, Na Han, Zhibo Zhang, Dekui Han, Zhong-Chao Guo, Zhikun Zhao, Qiang Li, Zongjin |
author_sort | Cao, Xiaocang |
collection | PubMed |
description | Background: Mesenchymal stem cell (MSC)-based therapies hold great promise for the treatment of inflammatory bowel disease (IBD). In order to optimize and maximize the therapeutic benefits of MSCs, we investigated whether cotransplantation of a chitosan (CS)-based injectable hydrogel with immobilized IGF-1 C domain peptide (CS-IGF-1C) and human placenta-derived MSCs (hP-MSCs) could ameliorate colitis in mice. Methods: IGF-1C hydrogel was generated by immobilizing IGF-1C to CS hydrogel. Colitis was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice. We initially applied hP-MSCs and CS-IGF-1C hydrogel for the treatment of colitis by in situ injection, and molecular imaging methods were used for real-time imaging of reactive oxygen species (ROS) and tracking of transplanted hP-MSCs by bioluminescence imaging (BLI). Furthermore, the effects of CS-IGF-1C hydrogel on prostaglandin E(2) (PGE(2)) secretion of hP-MSCs and polarization of M2 macrophages were investigated as well. Results: The CS-IGF-1C hydrogel significantly increased hP-MSC proliferation and promoted the production of PGE(2) from hP-MSCs in vitro. Moreover, in vivo studies indicated that the CS-IGF-1C hydrogel promoted hP-MSC survival as visualized by BLI and markedly alleviated mouse colitis, which was possibly mediated by hP-MSC production of PGE(2) and interleukin-10 (IL-10) production by polarized M2 macrophages. Conclusions: The CS-IGF-1C hydrogel improved the engraftment of transplanted hP-MSCs, ameliorated inflammatory responses, and further promoted the functional and structural recovery of colitis through PGE(2)-mediated M2 macrophage polarization. Molecular imaging approaches and therapeutic strategies for hydrogel application provide a versatile platform for exploring the promising therapeutic potential of MSCs in the treatment of IBD. |
format | Online Article Text |
id | pubmed-7359093 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-73590932020-07-17 IGF-1C hydrogel improves the therapeutic effects of MSCs on colitis in mice through PGE(2)-mediated M2 macrophage polarization Cao, Xiaocang Duan, Liyun Hou, Huixing Liu, Yue Chen, Shang Zhang, Shuaiqiang Liu, Yuanyuan Wang, Chen Qi, Xin Liu, Na Han, Zhibo Zhang, Dekui Han, Zhong-Chao Guo, Zhikun Zhao, Qiang Li, Zongjin Theranostics Research Paper Background: Mesenchymal stem cell (MSC)-based therapies hold great promise for the treatment of inflammatory bowel disease (IBD). In order to optimize and maximize the therapeutic benefits of MSCs, we investigated whether cotransplantation of a chitosan (CS)-based injectable hydrogel with immobilized IGF-1 C domain peptide (CS-IGF-1C) and human placenta-derived MSCs (hP-MSCs) could ameliorate colitis in mice. Methods: IGF-1C hydrogel was generated by immobilizing IGF-1C to CS hydrogel. Colitis was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice. We initially applied hP-MSCs and CS-IGF-1C hydrogel for the treatment of colitis by in situ injection, and molecular imaging methods were used for real-time imaging of reactive oxygen species (ROS) and tracking of transplanted hP-MSCs by bioluminescence imaging (BLI). Furthermore, the effects of CS-IGF-1C hydrogel on prostaglandin E(2) (PGE(2)) secretion of hP-MSCs and polarization of M2 macrophages were investigated as well. Results: The CS-IGF-1C hydrogel significantly increased hP-MSC proliferation and promoted the production of PGE(2) from hP-MSCs in vitro. Moreover, in vivo studies indicated that the CS-IGF-1C hydrogel promoted hP-MSC survival as visualized by BLI and markedly alleviated mouse colitis, which was possibly mediated by hP-MSC production of PGE(2) and interleukin-10 (IL-10) production by polarized M2 macrophages. Conclusions: The CS-IGF-1C hydrogel improved the engraftment of transplanted hP-MSCs, ameliorated inflammatory responses, and further promoted the functional and structural recovery of colitis through PGE(2)-mediated M2 macrophage polarization. Molecular imaging approaches and therapeutic strategies for hydrogel application provide a versatile platform for exploring the promising therapeutic potential of MSCs in the treatment of IBD. Ivyspring International Publisher 2020-06-19 /pmc/articles/PMC7359093/ /pubmed/32685014 http://dx.doi.org/10.7150/thno.45434 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Cao, Xiaocang Duan, Liyun Hou, Huixing Liu, Yue Chen, Shang Zhang, Shuaiqiang Liu, Yuanyuan Wang, Chen Qi, Xin Liu, Na Han, Zhibo Zhang, Dekui Han, Zhong-Chao Guo, Zhikun Zhao, Qiang Li, Zongjin IGF-1C hydrogel improves the therapeutic effects of MSCs on colitis in mice through PGE(2)-mediated M2 macrophage polarization |
title | IGF-1C hydrogel improves the therapeutic effects of MSCs on colitis in mice through PGE(2)-mediated M2 macrophage polarization |
title_full | IGF-1C hydrogel improves the therapeutic effects of MSCs on colitis in mice through PGE(2)-mediated M2 macrophage polarization |
title_fullStr | IGF-1C hydrogel improves the therapeutic effects of MSCs on colitis in mice through PGE(2)-mediated M2 macrophage polarization |
title_full_unstemmed | IGF-1C hydrogel improves the therapeutic effects of MSCs on colitis in mice through PGE(2)-mediated M2 macrophage polarization |
title_short | IGF-1C hydrogel improves the therapeutic effects of MSCs on colitis in mice through PGE(2)-mediated M2 macrophage polarization |
title_sort | igf-1c hydrogel improves the therapeutic effects of mscs on colitis in mice through pge(2)-mediated m2 macrophage polarization |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359093/ https://www.ncbi.nlm.nih.gov/pubmed/32685014 http://dx.doi.org/10.7150/thno.45434 |
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