Enhanced chondrogenic differentiation of iPS cell-derived mesenchymal stem/stromal cells via neural crest cell induction for hyaline cartilage repair
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- Zujur, Denise
- Center for iPS Cell Research and Application (CiRA), Kyoto University
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- Al-Akashi, Ziadoon
- Center for iPS Cell Research and Application (CiRA), Kyoto University
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- Nakamura, Anna
- Center for Regenerative Medicine Research, Faculty of Medicine, Saga University
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- Zhao, Chengzhu
- Center for iPS Cell Research and Application (CiRA), Kyoto University; Laboratory of Skeletal Development and Regeneration, Institute of Life Sciences, Chongqing Medical University
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- Takahashi, Kazuma
- Research Institute for Bioscience Product and Fine Chemicals, Ajinomoto Co., Inc
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- Aritomi, Shizuka
- Research Institute for Bioscience Product and Fine Chemicals, Ajinomoto Co., Inc
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- Theoputra, William
- Center for iPS Cell Research and Application (CiRA), Kyoto University
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- Kamiya, Daisuke
- Center for iPS Cell Research and Application (CiRA), Kyoto University; Takeda-CiRA Joint Program (T-CiRA)
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- Nakayama, Koichi
- Center for Regenerative Medicine Research, Faculty of Medicine, Saga University
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- Ikeya, Makoto
- Center for iPS Cell Research and Application (CiRA), Kyoto University; Takeda-CiRA Joint Program (T-CiRA)
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.
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.
Journal
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- Frontiers in Cell and Developmental Biology
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Frontiers in Cell and Developmental Biology 11 2023-05-10
Frontiers Media SA
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Keywords
Details 詳細情報について
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- CRID
- 1050015023021641600
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- ISSN
- 2296634X
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- HANDLE
- 2433/283299
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB