Abstract
Osteoarthritis (OA) is the most common type of arthritis and causes a significant deterioration in patients' quality of life. The high prevalence of OA as well as the current lack of disease-modifying drugs led to a rise in regenerative medicine efforts. The hope is that this will provide a treatment modality with the ability to alter the course of OA via structural modifications of damaged articular cartilage (AC). Regenerative therapy in OA starts with the concept that administered cells may engraft to a lesion site and differentiate into chondrocytes. However, recent studies show that cells, particularly when injected in suspension, rapidly undergo apoptosis after exerting a transient paracrine effect. If the injected stem cells do not lead to structural improvements of a diseased joint, the high cost of cell therapy for OA cannot be justified, particularly when compared with other injection therapeutics such as corticosteroids and hyaluronic acid. Long-term survival of implanted cells that offer prolonged paracrine effects or possible engraftment is essential for a successful cell therapy that will offer durable structural improvements. In this perspective review, the history and current status of regenerative therapy in OA are summarized along with the conceptual strategy and future directionsfor a successful regenerative therapy that can provide structural modifications in OA.