Towards one-stage cell-based treatment and non-invasive evaluation of cartilage defects

Abstract

The central aim of this thesis is to improve the clinical outcome of patients with a focal articular cartilage lesion treated with autologous chondrocyte implantation (ACI), by improvement of the surgical technique, the development of specific treatment algorithms and the evaluation and validation of suited outcome tools. Two surgeries in ACI are inevitable because the number of harvested cells is insufficient to directly fill the defect. As a consequence culture-expanded cells are reimplanted during a second surgery which creates a fibrocartilaginous tissue. This thesis shows that combining chondrocytes and MSCs positively influences cartilage-specific matrix production. This stimulation os most likely be initiated by trophic factors excreted by the MSC. Such a cell combination provides sufficient cells to fill the defect within one surgery. This one-stage cell-based treatment showed to be superior to microfracture treatment in goats. This thesis also shows that a new MRI technique (dGEMRIC) can validly be applied to evaluate the quality of cartilage regeneration where conventional MRI only provides information on defect fill. The last section of this thesis presents an evidence-based treatment algorithm which should preferably be used to select the proper treatment for your patient. Moreover, we also present patient characteristics that influence treatment outcome. These could be used to create realistic patient expectations prior to surgery. The clinical outcome of patients with a focal articular cartilage lesion can only be influenced by improvement of treatment selection, surgical therapy and outcome evaluation and by acknowledging that these factors are part of a larger process at which the patient and his characteristics play the leading role.