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タイトル: | Enhanced chondrogenic differentiation of iPS cell-derived mesenchymal stem/stromal cells via neural crest cell induction for hyaline cartilage repair |
著者: | Zujur, Denise Al-Akashi, Ziadoon Nakamura, Anna Zhao, Chengzhu Takahashi, Kazuma Aritomi, Shizuka Theoputra, William Kamiya, Daisuke Nakayama, Koichi Ikeya, Makoto |
著者名の別形: | 中村, アンナ 趙, 成珠 有富, 静 上谷, 大介 中山, 功一 池谷, 真 |
キーワード: | mesenchymal stem/stromal cells induced mesenchymal stem/stromal cells induced pluripotent stem cells chondrogenesis cartilage chondrocytes tissue engineering cell-based therapy |
発行日: | 10-May-2023 |
出版者: | Frontiers Media SA |
誌名: | Frontiers in Cell and Developmental Biology |
巻: | 11 |
論文番号: | 1140717 |
抄録: | Background: To date, there is no effective long-lasting treatment for cartilage tissue repair. Primary chondrocytes and mesenchymal stem/stromal cells are the most commonly used cell sources in regenerative medicine. However, both cell types have limitations, such as dedifferentiation, donor morbidity, and limited expansion. Here, we report a stepwise differentiation method to generate matrix-rich cartilage spheroids from induced pluripotent stem cell-derived mesenchymal stem/stromal cells (iMSCs) via the induction of neural crest cells under xeno-free conditions. Methods: The genes and signaling pathways regulating the chondrogenic susceptibility of iMSCs generated under different conditions were studied. Enhanced chondrogenic differentiation was achieved using a combination of growth factors and small-molecule inducers. Results: We demonstrated that the use of a thienoindazole derivative, TD-198946, synergistically improves chondrogenesis in iMSCs. The proposed strategy produced controlled-size spheroids and increased cartilage extracellular matrix production with no signs of dedifferentiation, fibrotic cartilage formation, or hypertrophy in vivo. Conclusion: These findings provide a novel cell source for stem cell-based cartilage repair. Furthermore, since chondrogenic spheroids have the potential to fuse within a few days, they can be used as building blocks for biofabrication of larger cartilage tissues using technologies such as the Kenzan Bioprinting method. |
記述: | iPS細胞由来の間葉系幹細胞から高品質な軟骨を作製. 京都大学プレスリリース. 2023-06-08. Generation of high-quality cartilage from iPS cell-derived mesenchymal stem cells. 京都大学プレスリリース. 2023-06-15. |
著作権等: | © 2023 Zujur, Al-Akashi, Nakamura, Zhao, Takahashi, Aritomi, Theoputra, Kamiya, Nakayama and Ikeya. 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/2433/283299 |
DOI(出版社版): | 10.3389/fcell.2023.1140717 |
PubMed ID: | 37234772 |
関連リンク: | https://www.cira.kyoto-u.ac.jp/j/pressrelease/news/230608-110000.html https://www.cira.kyoto-u.ac.jp/e/pressrelease/news/230615-130000.html |
出現コレクション: | 学術雑誌掲載論文等 |
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