Metabolism Regulates Phenotype of Inner Annulus Fibrosus Cells Within Tissue Engineered Constructs
Year: 2020
Type: dissertation
Abstract: Previous work has suggested a link between metabolism and inner annulus fibrosus (iAF) cell phenotype; however, tissue engineering approaches rarely consider the impact of cellular metabolism on matrix accumulation. It was hypothesized that growing iAF cells on multi-lamellar scaffolds in a low-glucose medium would activate a signalling pathway that would allow the cells to maintain their phenotype, thereby contributing to a more functionally appropriate ECM. iAF tissues grown in low-glucose maintained their native phenotype and showed activation of the AMPK-PGC-1α-Sox9 signalling axis. Inhibition of PGC-1α led to a loss of the iAF cell phenotype demonstrating a link between phenotype and metabolism. Exogenous ATP and salicylate treatment led to increased tissue accumulation but loss of the iAF phenotype. These studies have provided novel insights into the pathways that regulate the iAF phenotype within tissue engineered constructs, and whose findings may facilitate the identification of the conditions needed for IVD tissue regeneration.
Source: TSpace (University of Toronto)
Author: Raeesa Matadar
Language: English
Subfield: Orthopedics and Sports Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3162594774