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

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 limi...

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Published in:Frontiers in cell and developmental biology 2023-05, Vol.11, p.1140717-1140717
Main Authors: Zujur, Denise, Al-Akashi, Ziadoon, Nakamura, Anna, Zhao, Chengzhu, Takahashi, Kazuma, Aritomi, Shizuka, Theoputra, William, Kamiya, Daisuke, Nakayama, Koichi, Ikeya, Makoto
Format: Article
Language:English
Subjects:
cartilage
Cell and Developmental Biology
chondrocytes
chondrogenesis
induced mesenchymal stem/stromal cells
induced pluripotent stem cells
mesenchymal stem/stromal cells
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Summary: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. 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. 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 . 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.
ISSN:2296-634X
2296-634X
DOI:10.3389/fcell.2023.1140717