Immunity-and-matrix-regulatory cells promote hyaline-like cartilage repair in osteoarthritis.

Articular cartilage repair in osteoarthritis (OA) remains a major clinical challenge. Although approaches using mesenchymal stem cells (MSCs) have demonstrated partial efficacy in OA, the regenerated tissue is often unable to form stable hyaline-like cartilage phenotype. Here, we introduce immunity-and-matrix-regulatory cells (IMRCs), derived from human embryonic stem cells (ESCs), as an alternative cell source for OA therapy. Using a multiple-level platform including 2D chondrocytes, 3D OA cartilage organoids (OCOs), rabbit cartilage explants, and a rat OA model, we demonstrate that IMRCs significantly enhance hyaline-like matrix formation while suppressing inflammation, angiogenesis, and fibrotic remodeling. Mechanistically, IMRC-mediated cartilage repair is partially associated with MMP1-dependent matrix remodeling. This study establishes a translational evaluation strategy for IMRCs and points to their potential as an alternative cell source for inducing cartilage repair in OA. Notably, the OCOs established in this study provide a pathologically relevant in vitro platform for evaluating cartilage regeneration in OA.