Clinical-grade iPSC-derived chondrogenic micropellets for treating advanced cartilage defects.

Abstract

Induced pluripotent stem cell (iPSC)-derived chondrogenic tissues represent a promising alternative for treating cartilage defects in chronic degenerative joint conditions such as osteoarthritis (OA). Cartilage tissue has limited self-repair capacity, and although allogeneic transplantation has potential, a less invasive delivery method could enhance the efficacy of cell-based therapies. The aim of this study was to develop iPSC-derived "minimal injectable unit" chondrogenic micropellets (MIUChons) for delivery via intra-articular injections for OA therapy. To create transplantable allogeneic cartilage tissue, we optimized good manufacturing practice or clinical-grade production of iPSC-derived injectable chondrogenic spheroids and tested them in OA animal models. MIUChons were delivered to damaged cartilage through a single injection. In vivo and in vitro analyses demonstrated that MIUChon treatment effectively reduced cartilage degeneration and deterioration. In addition, injecting MIUChons into the intra-articular cavity improved arthritis symptoms. Overall, MIUChons offer a strategy for treating cartilage deterioration via intra-articular injection in patients with OA.