Long-term evaluation of human iPSC-derived cartilage for repairing chondral defects.

Induced pluripotent stem cells (iPSCs) have demonstrated superior capacity to regenerate hyaline cartilage compared to mesenchymal stromal cells (MSCs). However, most previous animal studies have only conducted short-term assessments. We performed a long-term (8 weeks) in vitro chondrogenesis of human iPSC-derived multipotent progenitor cells (iMPCs) and human MSCs. The expression levels of hypertrophy-related genes were significantly lower in the iMPC group compared to the MSC group, such as collagen type X being 5-fold lower on day 56. In the animal study, implants from the iMPC group maintained more matrix than the MSC group at both short and long-term time points (12 and 48 weeks). Importantly, at 48 weeks, the native cartilage surrounding the defect areas in some rats from the MSC group showed severe degradation, which was not observed in the iMPC group. In conclusion, iMPCs represent a safe and effective cell source for long-term hyaline cartilage repair.