Abstract
Intervertebral disc (IVD) degeneration presents a harsh microenvironment characterised by low glucose, low oxygen and matrix acidity posing a significant challenge for cell-based therapies. The objective of this work was to assess the effect of primed bone marrow derived stem cells (BMSC) and articular chondrocytes (AC) in different pH (7.1, 6.8 and 6.5) conditions and assess metabolic activity in terms of oxygen (O2) and glucose consumption as well as lactate production. Secondly, we investigated pH effects on cell viability and matrix accumulation capacity. Primary cells were encapsulated in alginate beads and cultured in disc-like conditions (5% O2, 5mM glucose, pH 7.1, 6.8 and 6.5). For growth factor priming, cells were cultured with 10ng/ml TGF-β3 at a pH of 7.4 for 14 days prior to being subjected to acidic pH conditions. AC exhibited superior cell viability and sGAG deposition compared to BMSC at all pH levels which was further enhanced after priming. Priming also reduced O2 consumption of AC for all pH conditions while lactate production profiles of both cell types were altered with decreasing extracellular pH. This work demonstrates the importance of cell type selection to sustain disc-like microenvironmental conditions. Results show that BMSCs that have not been primed may need additional factors to sustain the harsh acidic microenvironment. In contrast, AC were capable of sustaining the low pH conditions better than BMSC and accumulated more similar disc-like matrix in all conditions. Overall this study highlights that AC may be advantageous for disc regeneration and warrant further investigation for disc repair.
