Despite overwhelming need, with about 9 million osteoarthritis (OA) sufferers in UK alone, little progress has been made towards pathogenesis-based categorising of patients and subsequent intervention. Experimental studies relied heavily on animal models, which is inefficient and expensive, and has often produced drugs failing in phase I/II clinical trials due to off-target side effects or failure to predict human disease in animal models. This project aims to address this challenge by developing a scalable in vitro human organotypic tissue model. The model can be used to simulate OA processes and ultimately, exploited to seek biomarkers for early diagnosis or screen potential drugs for efficacy.
We have previously shown that a stratified 3D-tissue akin of articular cartilage can be generated over a 35-day period using a tissue engineering approach with primary human chondrocyte progenitor cells. The engineered tissue mimics native cartilage both in structural organization and biochemical composition. Here, we explore the influence of the nature and homogeneity of initial cell population on cartilage development and maturation.
Cell commitment to chondrogenic lineage was found to be a pre-requisite for induction of appropriate appositional growth and stratification of cartilage. Fully differentiated chondrocytes failed to produce a zonated, cartilage-like matrix. Immortalized clonal cell lines were generated, and these were capable of reproducing an appropriate tissue architecture, showing that tissue formation depends on a single progenitor.
These findings not only enable generation of human tissue at scale in a highly controlled way, but open up the possibility to consider developmental positional information or genetics within our model.