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Enhanced chondrogenic differentiation of iPS cell-derived mesenchymal stem/stromal cells via neural crest cell induction for hyaline cartilage repair

発表形態:
原著論文
主要業績:
主要業績
単著・共著:
共著
発表年月:
2023年05月
DOI:
10.3389/fcell.2023.1140717
会議属性:
指定なし
査読:
有り
リンク情報:

日本語フィールド

著者:
*Zujur D, Al-Akashi Z, Nakamura A, Zhao C, Takahashi K, Aritomi S, Theoputra W, Kamiya D, Nakayama K, Ikeya M
題名:
Enhanced chondrogenic differentiation of iPS cell-derived mesenchymal stem/stromal cells via neural crest cell induction for hyaline cartilage repair
発表情報:
Front Cell Dev Biol 巻: 11 ページ: 1140717
キーワード:
cartilage; cell-based therapy; chondrocytes; chondrogenesis; induced mesenchymal stem/stromal cells; induced pluripotent stem cells; mesenchymal stem/stromal cells; tissue engineering
概要:
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.
抄録:

英語フィールド

Author:
*Zujur D, Al-Akashi Z, Nakamura A, Zhao C, Takahashi K, Aritomi S, Theoputra W, Kamiya D, Nakayama K, Ikeya M
Title:
Enhanced chondrogenic differentiation of iPS cell-derived mesenchymal stem/stromal cells via neural crest cell induction for hyaline cartilage repair
Announcement information:
Front Cell Dev Biol Vol: 11 Page: 1140717
Keyword:
cartilage; cell-based therapy; chondrocytes; chondrogenesis; induced mesenchymal stem/stromal cells; induced pluripotent stem cells; mesenchymal stem/stromal cells; tissue engineering
An abstract:
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.


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