Knee Culture of Tissue (KCoT)
Research type
Research Study
Full title
Development of a knee tissue culture model to study human joint disease
IRAS ID
325887
Contact name
Nicholas Kalson
Contact email
Sponsor organisation
Northumbria Healthcare NHS Foundation Trust
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Ex vivo human tissue models offer a translational bridge between basic research and in vivo human clinical studies. Culture models provide tools to investigate normal tissue function, examine disease pathogenesis and provide a platform for drug discovery.
Currently ex vivo human models of rheumatological and orthopaedic joint disease are limited to cell isolation and two-dimensional (2D) culture. However, 2D culture does not accurately recreate the complex human tissue architecture and lack cell-cell & cell-matrix interactions, limiting the translational relevance of experimental findings. Because of these limitations, our team in the Newcastle Fibrosis Research Group, led by Dr Lee Borthwick, have developed a culture model in which human tissue slices remain viable for ~7 days and maintain ‘normal’ healthy tissue metabolism 1. This culture model has since been extensively validated in several organs, including lung, liver, kidney and heart (1 2).
In this study we will test whether our 3D tissue slice culture ‘bioreactor’ can be used to keep knee joint synovium alive. This would provide a tractable experimental platform, for improving our understanding of disease pathology and for pre-clinical testing of novel therapeutic agents.
If we demonstrate success in part one of the study, we will then proceed to further collection of knee tissue for ongoing studies using the tissue culture bioreactor.
1. Paish, H. L. et al. A Bioreactor Technology for Modeling Fibrosis in Human and Rodent Precision-Cut Liver Slices. Hepatology 70, 1377–1391 (2019).
2. Leitch, A. C. et al. Renal injury and hepatic effects from the methylimidazolium ionic liquid M8OI in mouse. Ecotoxicol Environ Saf 202, 110902 (2020).REC name
North of Scotland Research Ethics Committee 2
REC reference
23/NS/0045
Date of REC Opinion
2 May 2023
REC opinion
Favourable Opinion