Mesenchymal stem cells exert renoprotection via extracellular vesicle-mediated modulation of M2 macrophages and spleen-kidney network

Adipose-derived mesenchymal stem cells (ASCs) have shown therapeutic potentials against refractory diseases. However, the detailed therapeutic mechanisms remain unclear. Here, we report the therapeutic actions of human ASCs in nephritis, focusing on cellular dynamics and multi-organ networks. Intrav...

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Autores principales: Shimamura, Yuko, Furuhashi, Kazuhiro, Tanaka, Akihito, Karasawa, Munetoshi, Nozaki, Tomoya, Komatsu, Shintaro, Watanabe, Kenshi, Shimizu, Asuka, Minatoguchi, Shun, Matsuyama, Makoto, Sawa, Yuriko, Tsuboi, Naotake, Ishimoto, Takuji, Suzuki, Hiroshi I., Maruyama, Shoichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334610/
https://www.ncbi.nlm.nih.gov/pubmed/35902687
http://dx.doi.org/10.1038/s42003-022-03712-2
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author Shimamura, Yuko
Furuhashi, Kazuhiro
Tanaka, Akihito
Karasawa, Munetoshi
Nozaki, Tomoya
Komatsu, Shintaro
Watanabe, Kenshi
Shimizu, Asuka
Minatoguchi, Shun
Matsuyama, Makoto
Sawa, Yuriko
Tsuboi, Naotake
Ishimoto, Takuji
Suzuki, Hiroshi I.
Maruyama, Shoichi
author_facet Shimamura, Yuko
Furuhashi, Kazuhiro
Tanaka, Akihito
Karasawa, Munetoshi
Nozaki, Tomoya
Komatsu, Shintaro
Watanabe, Kenshi
Shimizu, Asuka
Minatoguchi, Shun
Matsuyama, Makoto
Sawa, Yuriko
Tsuboi, Naotake
Ishimoto, Takuji
Suzuki, Hiroshi I.
Maruyama, Shoichi
author_sort Shimamura, Yuko
collection PubMed
description Adipose-derived mesenchymal stem cells (ASCs) have shown therapeutic potentials against refractory diseases. However, the detailed therapeutic mechanisms remain unclear. Here, we report the therapeutic actions of human ASCs in nephritis, focusing on cellular dynamics and multi-organ networks. Intravenously-administered ASCs accumulated in spleen but not kidneys. Nevertheless, ASCs increased M2 macrophages and Tregs in kidneys and drove strong renoprotection. Splenectomy abolished these therapeutic effects. ASC-derived extracellular vesicles (EVs) were transferred to M2 macrophages, which entered the bloodstream from spleen. EVs induced the transcriptomic signatures of hyperpolarization and PGE2 stimulation in M2 macrophages and ameliorated glomerulonephritis. ASCs, ASC-derived EVs, and EV-transferred M2 macrophages enhanced Treg induction. These findings suggest that EV transfer from spleen-accumulated ASCs to M2 macrophages and subsequent modulation of renal immune-environment underlie the renoprotective effects of ASCs. Our results provide insights into the therapeutic actions of ASCs, focusing on EV-mediated modulation of macrophages and the spleen-kidney immune network.
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spelling pubmed-93346102022-07-30 Mesenchymal stem cells exert renoprotection via extracellular vesicle-mediated modulation of M2 macrophages and spleen-kidney network Shimamura, Yuko Furuhashi, Kazuhiro Tanaka, Akihito Karasawa, Munetoshi Nozaki, Tomoya Komatsu, Shintaro Watanabe, Kenshi Shimizu, Asuka Minatoguchi, Shun Matsuyama, Makoto Sawa, Yuriko Tsuboi, Naotake Ishimoto, Takuji Suzuki, Hiroshi I. Maruyama, Shoichi Commun Biol Article Adipose-derived mesenchymal stem cells (ASCs) have shown therapeutic potentials against refractory diseases. However, the detailed therapeutic mechanisms remain unclear. Here, we report the therapeutic actions of human ASCs in nephritis, focusing on cellular dynamics and multi-organ networks. Intravenously-administered ASCs accumulated in spleen but not kidneys. Nevertheless, ASCs increased M2 macrophages and Tregs in kidneys and drove strong renoprotection. Splenectomy abolished these therapeutic effects. ASC-derived extracellular vesicles (EVs) were transferred to M2 macrophages, which entered the bloodstream from spleen. EVs induced the transcriptomic signatures of hyperpolarization and PGE2 stimulation in M2 macrophages and ameliorated glomerulonephritis. ASCs, ASC-derived EVs, and EV-transferred M2 macrophages enhanced Treg induction. These findings suggest that EV transfer from spleen-accumulated ASCs to M2 macrophages and subsequent modulation of renal immune-environment underlie the renoprotective effects of ASCs. Our results provide insights into the therapeutic actions of ASCs, focusing on EV-mediated modulation of macrophages and the spleen-kidney immune network. Nature Publishing Group UK 2022-07-28 /pmc/articles/PMC9334610/ /pubmed/35902687 http://dx.doi.org/10.1038/s42003-022-03712-2 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
Shimamura, Yuko
Furuhashi, Kazuhiro
Tanaka, Akihito
Karasawa, Munetoshi
Nozaki, Tomoya
Komatsu, Shintaro
Watanabe, Kenshi
Shimizu, Asuka
Minatoguchi, Shun
Matsuyama, Makoto
Sawa, Yuriko
Tsuboi, Naotake
Ishimoto, Takuji
Suzuki, Hiroshi I.
Maruyama, Shoichi
Mesenchymal stem cells exert renoprotection via extracellular vesicle-mediated modulation of M2 macrophages and spleen-kidney network
title Mesenchymal stem cells exert renoprotection via extracellular vesicle-mediated modulation of M2 macrophages and spleen-kidney network
title_full Mesenchymal stem cells exert renoprotection via extracellular vesicle-mediated modulation of M2 macrophages and spleen-kidney network
title_fullStr Mesenchymal stem cells exert renoprotection via extracellular vesicle-mediated modulation of M2 macrophages and spleen-kidney network
title_full_unstemmed Mesenchymal stem cells exert renoprotection via extracellular vesicle-mediated modulation of M2 macrophages and spleen-kidney network
title_short Mesenchymal stem cells exert renoprotection via extracellular vesicle-mediated modulation of M2 macrophages and spleen-kidney network
title_sort mesenchymal stem cells exert renoprotection via extracellular vesicle-mediated modulation of m2 macrophages and spleen-kidney network
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334610/
https://www.ncbi.nlm.nih.gov/pubmed/35902687
http://dx.doi.org/10.1038/s42003-022-03712-2
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