AbstractOsteoarthritis (OA) is characterized by joint pain and impairment due to cartilage degradation and is one of the most common forms of musculo-skeletal disease in the world. The initiation of OA is unknown but age, obesity and trauma as well as genetic factors combined with low-grade inflammation play important roles. No early diagnostic biomarker is available and no disease modifying treatment exists except for autologous chondrocyte transplantation (ACT/ACI) developed by our group for treatment of focal cartilage defects. In this presentation the transition of the ACI technology from animal studies to an ATMP product over a 30 year period will be discussed as well the excellent long term clinical results. The challenges for future will be based on improvement of the ACT technology towards biological resurfacing. One such option could be the derivation of chondroprogenitor donor cell lines from induced pluripotent stem cell lines established from human cartilage (c-iPS cells) combined with automated cell culturing. Furthermore, the need of a deeper understanding of cartilage regeneration mechanisms and development of better diagnostic tools for early OA will be addressed.