Enhancing the hyaline cartilage regenerative potential of induced pluripotent stem cell-derived chondrocyte cell sheets

This study aimed to develop a method for creating chondrocyte cell sheets from human induced pluripotent stem cells (iPS cells) as a viable alternative to conventional methods. Researchers generated cartilaginous tissue from iPS cells and used isolated chondrocytes to create the sheets. The sheets were produced using different conditions, including varying serum concentrations and oxygen levels, and were compared to polydactyly-derived chondrocyte (PDC) sheets.

In Phase 1, the researchers found that hypoxic/high-seeding-density culture conditions improved the chondrogenic properties of the iPS cell-derived sheets. However, when the sheets were transplanted, the iPS cell-derived sheets resulted in fibrotic repair tissue, while the PDC sheets produced hyaline-like cartilage. In Phase 2, the researchers evaluated the iPS cell-derived sheets using low-serum medium and hypoxic/high-seeding-density culture conditions.

They discovered that these conditions increased the expression of cartilage-related genes, such as collagen type II alpha 1 (COL2A1) and SRY-box transcription factor 9 (SOX9). Additionally, the sheets secreted transforming growth factor beta 1 and melanoma inhibitory activity, and upregulated several cell surface markers.

These conditions led to the regeneration of hyaline cartilage in the iPS cell-derived sheets at 4 weeks, and this repair tissue remained stable at 12 weeks without any bone formation. The study concludes that creating a robust fabrication protocol enabled human iPS cell-derived chondrocyte sheets to regenerate hyaline-like cartilage in vivo. This finding suggests that these cells have the potential to be a scalable cell source for clinical cartilage repair, offering a promising alternative to current methods.