Advancing cartilage cell therapy through chondrocyte culture and patient reported outcome measures (PROMs)

Sykes, Jessica Grace

Abstract

Autologous chondrocyte implantation (ACI) is the only UK approved cell therapy or knee cartilage defects which might otherwise progress to osteoarthritis. For ACI, chondrocytes isolated from a healthy cartilage biopsy are expanded in number prior to their re-implantation into the damaged joint. ACI is costeffective compared to alternative surgical interventions but it comes with a 50% failure rate at 10 years. Making ACI truly successful requires optimisation. Possible enhancements include improvement of the chondrogenic capacity of chondrocytes and better monitoring of the clinical outcomes.
Herein, we histologically, metabolically and biochemically compared chondrocytes sourced from the ankle and knee. We found that chondrocytes sourced from ankle cartilage exhibited higher chondrogenic potential metabolically and histologically, irrespective of external stimuli.
In separate experiments, we characterised the extracellular matrix (ECM) of chondrocytes cultured in Stemulate™ to determine whether it could be used to improve upon the existing ACI protocol. While Stemulate™ was effective at increasing chondrocyte monolayer proliferation, it impacted upon the redifferentiation potential.
To assess clinical outcome of ankle surgery and ACI we developed a brand new patient-reported outcome measure and performed validation analyses to screen a cohort of 206 participants. It demonstrated proven reliability, responsiveness and good correlation with existing scores. In clinic, our foot and ankle clinicians are using it to monitor clinical outcomes.

Citation

Sykes, J. G. (2019). Advancing cartilage cell therapy through chondrocyte culture and patient reported outcome measures (PROMs). (Thesis). Keele University. Retrieved from https://keele-repository.worktribe.com/output/414327

• Thesis Type: Thesis
• Publicly Available Date: May 26, 2023
• Public URL: https://keele-repository.worktribe.com/output/414327
• Award Date: 2019-06