Cell therapy to treat knee cartilage defects - transcriptome exploration of autologous mesenchymal stromal cells and chondrocytes

Tierney, Lauren Jessica

Abstract

Autologous chondrocyte implantation (ACI) has repeatedly been shown to be an effective treatment for cartilage defects within the knee and can delay or prevent the need for a total knee replacement. However, the level of clinical benefit experienced varies between patients; for this reason, research efforts have been focused on further optimising this procedure. Optimisation of the cell source used, is one such area of research. The ASCOT trial is currently underway, to directly compare the outcome of patients treated with chondrocytes, MSCs or a combination of the two. This research project explores the miRNA and mRNA content of the cells used during the ASCOT trial and relates these transcriptomic profiles to a selection of post-operative clinical outcome measures with the aim of identifying cell therapy potency markers and to gain insight into their mode of action. This research has identified a panel of genes related to post-surgical success, which are outcome measure specific. Interestingly, the majority of the biological pathways that were predicted to be differentially regulated between patients with a favourable vs unfavourable post-operative outcomes related to immunological functioning. Further analyses were conducted which explored the genetic stability of the autologous culture expanded cells used during the ASCOT trial, this analysis suggested the presence of a mosaic population of aberrant cells in a small number of samples. Lastly the project developed a mixed multilevel model which took follow-up data, for as long as 23 years, from patients treated with ACI. This found that patients with high pre-operative score, younger age at the time of ACI, lower cell number implanted, specific defect locations and low defect grades were related to higher functional knee scores post-ACI.

Citation

Tierney, L. J. (2024). Cell therapy to treat knee cartilage defects - transcriptome exploration of autologous mesenchymal stromal cells and chondrocytes. (Thesis). Keele University. Retrieved from https://keele-repository.worktribe.com/output/775433

• Thesis Type: Thesis
• Deposit Date: Mar 14, 2024
• Public URL: https://keele-repository.worktribe.com/output/775433
• Additional Information: Embargo on access until 1 March 2027 - The thesis includes information that was obtained under a promise of confidentiality.
• Award Date: 2024-03