Development of the human ex vivo split tissue osteoarthritis model

Abstract

Osteoarthritis (OA) is a disease characterized by loss of functional articular cartilage with associated whole-joint pathology and resultant pain and disability, which is projected to affect 59.4 million Americans by 2020. As such, our laboratory has set out to develop valid and clinically applicable models to unravel disease mechanisms and evaluate potential treatments for OA utilizing cartilage explants obtained from tissues discarded after standard-of-care joint surgeries. This translational modeling approach is leading to the identification of targets for prevention and treatment, as well as biomarkers for early diagnosis, disease staging, prognostication and treatment monitoring. Due to significant patient to patient and intra-joint variability in OA development, there is a need for more standardized sampling and culturing strategies for spontaneous OA ex vivo modeling. Therefore, osteoarthritic articular cartilage was obtained from total knee arthroplasty and osteochondral allograft transplantation patients. Cartilage explants were then cut into halves and cultured individually. The objectives of this study were to validate consistency of relevant biomarker production between halves of osteoarthritic cartilage explants, and to determine if candidate biomarkers can be detected in human osteoarthritic cartilage explant cultures for subsequent therapeutic screening studies. A secondary focus of this study was to evaluate the disease-modifying capabilities of two clinically used therapeutics utilizing this model. We hypothesize that this 'split!tissue' approach will control for variability in the development and progression of OA through validation of consistency between cartilage explant halves and subsequent therapeutic screening.