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タイトル: | Immunosuppressants Tacrolimus and Sirolimus revert the cardiac antifibrotic properties of p38-MAPK inhibition in 3D-multicellular human iPSC-heart organoids |
著者: | Tian, Yu Tsujisaka, Yuta Li, Vanessa Y. Tani, Kanae Lucena-Cacace, Antonio Yoshida, Yoshinori https://orcid.org/0000-0001-5511-9090 (unconfirmed) |
著者名の別形: | 田, 雨 辻坂, 勇太 谷, 奏慧 吉田, 善紀 |
キーワード: | heart organoid sirolimus tacrolimus p38 cardiac fibroblasts fibrosis SB202190 |
発行日: | 11-Nov-2022 |
出版者: | Frontiers Media SA |
誌名: | Frontiers in Cell and Developmental Biology |
巻: | 10 |
論文番号: | 1001453 |
抄録: | Cardiac reactive fibrosis is a fibroblast-derived maladaptive process to tissue injury that exacerbates an uncontrolled deposition of large amounts of extracellular matrix (ECM) around cardiomyocytes and vascular cells, being recognized as a pathological entity of morbidity and mortality. Cardiac fibrosis is partially controlled through the sustained activation of TGF-β1 through IL-11 in fibroblasts. Yet, preclinical studies on fibrosis treatment require human physiological approaches due to the multicellular crosstalk between cells and tissues in the heart. Here, we leveraged an iPSC-derived multi-lineage human heart organoid (hHO) platform composed of different cardiac cell types to set the basis of a preclinical model for evaluating drug cardiotoxicity and assessing cardiac fibrosis phenotypes. We found that the inhibition of the p38-MAPK pathway significantly reduces COL1A1 depositions. Yet, concomitant treatment with organ-rejection immunosuppressant drugs Tacrolimus or Sirolimus reverts this effect, opening new questions on the clinical considerations of combined therapies in reducing fibrosis after organ transplantation. |
記述: | Immunosuppressive regimens after a heart transplant can hamper good therapeutic progressions in fibrosis. 京都大学プレスリリース. 2022-11-15. より本物の心臓に近い心臓オルガノイドによる薬剤の効果を評価するシステム --細胞間コミュニケーションを研究できるツールの開発--. 京都大学プレスリリース. 2022-11-21. |
著作権等: | © 2022 Tian, Tsujisaka, Li, Tani, Lucena-Cacace and Yoshida. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
URI: | http://hdl.handle.net/2433/277269 |
DOI(出版社版): | 10.3389/fcell.2022.1001453 |
PubMed ID: | 36438566 |
関連リンク: | https://www.cira.kyoto-u.ac.jp/e/pressrelease/news/221115-130000.html https://www.cira.kyoto-u.ac.jp/j/pressrelease/news/221121-150000.html |
出現コレクション: | 学術雑誌掲載論文等 |
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