Abstract Knee osteoarthritis is a degenerative joint disease, with no fundamental cure beyond pain relief and anti-inflammation. This phase I, multicenter, open-label, dose-escalation trial evaluated the safety, tolerability, and preliminary efficacy of OSCA, an intra-articular injection co-formulation of osiramestrocel (allogeneic mesenchymal stromal cells) and cartilage acellular matrix, in patients with Kellgren–Lawrence (K&L) grade 2 or 3 knee osteoarthritis.