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Ferroptotic MSCs protect mice against sepsis via promoting macrophage efferocytosis
The therapeutic effect of mesenchymal stem cells (MSCs) on sepsis has been well-known. However, a comprehensive understanding of the relationship between MSCs and macrophages remains elusive. Superparamagnetic iron oxide (SPIO) is one of the most commonly used tracers for MSCs. Our previous study ha...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9512818/ https://www.ncbi.nlm.nih.gov/pubmed/36163182 http://dx.doi.org/10.1038/s41419-022-05264-z |
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author | Pan, Yuchen Li, Jingman Wang, Jiali Jiang, Qi Yang, Jingjing Dou, Huan Liang, Huaping Li, Kuanyu Hou, Yayi |
author_facet | Pan, Yuchen Li, Jingman Wang, Jiali Jiang, Qi Yang, Jingjing Dou, Huan Liang, Huaping Li, Kuanyu Hou, Yayi |
author_sort | Pan, Yuchen |
collection | PubMed |
description | The therapeutic effect of mesenchymal stem cells (MSCs) on sepsis has been well-known. However, a comprehensive understanding of the relationship between MSCs and macrophages remains elusive. Superparamagnetic iron oxide (SPIO) is one of the most commonly used tracers for MSCs. Our previous study has shown that SPIO enhanced the therapeutic effect of MSCs in a macrophage-dependent manner. However, the fate of SPIO-labeled MSCs (MSC(SPIO)) after infusion remains unknown and the direct interaction between MSC(SPIO) and macrophages remains unclear. Mice were injected intravenously with MSC(SPIO) at 2 h after Escherichia coli infection and sacrificed at different times to investigate their distribution and therapeutic effect. We found that MSC(SPIO) homed to lungs rapidly after infusion and then trapped in livers for more than 10 days. Only a few MSC(SPIO) homed to the spleen and there was no MSC(SPIO) detectable in the brain, heart, kidney, colon, and uterus. MSC(SPIO) tended to stay longer in injured organs compared with healthy organs and played a long-term protective role in sepsis. The mRNA expression profiles between MSCs and MSC(SPIO) were rather different, genes related to lipid metabolism, inflammation, and oxidative stress were changed. The levels of ROS and lipid peroxide were elevated in MSC(SPIO), which confirmed that SPIO-induced ferroptosis in MSC(SPIO). Ferroptosis of MSC(SPIO) induced by SPIO enhanced the efferocytosis of macrophages and thus enhanced the protective effect on septic mice, while the benefits were impaired after MSC(SPIO) were treated with Ferrostatin-1 (Fer-1) or Liproxtatin-1 (Lip-1), the inhibitors of ferroptosis. SPIO-induced ferroptosis in MSCs contributes to better therapeutic effects in sepsis by enhancing the efferocytosis of macrophages. Our data showed the efficacy and advantage of MSC(SPIO) as a therapeutic tool and the cell states exert different curative effects on sepsis. |
format | Online Article Text |
id | pubmed-9512818 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-95128182022-09-27 Ferroptotic MSCs protect mice against sepsis via promoting macrophage efferocytosis Pan, Yuchen Li, Jingman Wang, Jiali Jiang, Qi Yang, Jingjing Dou, Huan Liang, Huaping Li, Kuanyu Hou, Yayi Cell Death Dis Article The therapeutic effect of mesenchymal stem cells (MSCs) on sepsis has been well-known. However, a comprehensive understanding of the relationship between MSCs and macrophages remains elusive. Superparamagnetic iron oxide (SPIO) is one of the most commonly used tracers for MSCs. Our previous study has shown that SPIO enhanced the therapeutic effect of MSCs in a macrophage-dependent manner. However, the fate of SPIO-labeled MSCs (MSC(SPIO)) after infusion remains unknown and the direct interaction between MSC(SPIO) and macrophages remains unclear. Mice were injected intravenously with MSC(SPIO) at 2 h after Escherichia coli infection and sacrificed at different times to investigate their distribution and therapeutic effect. We found that MSC(SPIO) homed to lungs rapidly after infusion and then trapped in livers for more than 10 days. Only a few MSC(SPIO) homed to the spleen and there was no MSC(SPIO) detectable in the brain, heart, kidney, colon, and uterus. MSC(SPIO) tended to stay longer in injured organs compared with healthy organs and played a long-term protective role in sepsis. The mRNA expression profiles between MSCs and MSC(SPIO) were rather different, genes related to lipid metabolism, inflammation, and oxidative stress were changed. The levels of ROS and lipid peroxide were elevated in MSC(SPIO), which confirmed that SPIO-induced ferroptosis in MSC(SPIO). Ferroptosis of MSC(SPIO) induced by SPIO enhanced the efferocytosis of macrophages and thus enhanced the protective effect on septic mice, while the benefits were impaired after MSC(SPIO) were treated with Ferrostatin-1 (Fer-1) or Liproxtatin-1 (Lip-1), the inhibitors of ferroptosis. SPIO-induced ferroptosis in MSCs contributes to better therapeutic effects in sepsis by enhancing the efferocytosis of macrophages. Our data showed the efficacy and advantage of MSC(SPIO) as a therapeutic tool and the cell states exert different curative effects on sepsis. Nature Publishing Group UK 2022-09-26 /pmc/articles/PMC9512818/ /pubmed/36163182 http://dx.doi.org/10.1038/s41419-022-05264-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Pan, Yuchen Li, Jingman Wang, Jiali Jiang, Qi Yang, Jingjing Dou, Huan Liang, Huaping Li, Kuanyu Hou, Yayi Ferroptotic MSCs protect mice against sepsis via promoting macrophage efferocytosis |
title | Ferroptotic MSCs protect mice against sepsis via promoting macrophage efferocytosis |
title_full | Ferroptotic MSCs protect mice against sepsis via promoting macrophage efferocytosis |
title_fullStr | Ferroptotic MSCs protect mice against sepsis via promoting macrophage efferocytosis |
title_full_unstemmed | Ferroptotic MSCs protect mice against sepsis via promoting macrophage efferocytosis |
title_short | Ferroptotic MSCs protect mice against sepsis via promoting macrophage efferocytosis |
title_sort | ferroptotic mscs protect mice against sepsis via promoting macrophage efferocytosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9512818/ https://www.ncbi.nlm.nih.gov/pubmed/36163182 http://dx.doi.org/10.1038/s41419-022-05264-z |
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