Next-generation therapies for osteoarthritis: the evolving role of cell therapy products

Osteoarthritis (OA) remains a major cause of disability worldwide; however, current non-surgical treatments offer transient symptom relief without altering disease course. This leaves a therapeutic gap for patients with early-to-moderate disease who are not candidates for surgery but continue to experience pain and functional limitation. Intra-articular interventions such as non-steroidal anti-inflammatory drugs, hyaluronic acid, and platelet-rich plasma may ease symptoms, but do not modify disease progression. By contrast, cell therapy products hold promise as regenerative approaches that may both alleviate pain and influence disease trajectory. Cell therapy products for knee OA exert multimodal effects through paracrine and immunomodulatory mechanisms, including modulation of synovial inflammation, attenuation of senescence-associated pathways, and support of extracellular matrix production. Despite encouraging preclinical and clinical signals, only a few cell therapy products have been approved globally, and most remain in development. However, substantial translational challenges remain, including variability in cell source and potency, limited persistence in joint environment, small clinical trial sizes, and regulatory and manufacturing hurdles. To achieve broader adoption, it will be essential to demonstrate superiority to minimally manipulated orthobiologics, clarify redosing strategies, and generate robust long-term evidence. This Review discusses recent clinical trial data, mechanistic insights, regulatory considerations, and operational challenges shaping the evolving role of cell therapy products for OA as next-generation candidates to bridge the gap between pharmacological and surgical interventions. In addition, this Review is written to support regulatory agencies as well as academics and clinicians involved in the development and evaluation of cell therapy products.