Characterisation of a divergent progenitor cell sub-populations in human osteoarthritic cartilage: the role of telomere erosion and replicative senescence

Abstract

In recent years it has become increasingly clear that articular cartilage harbours a viable pool of progenitor cells and interest has focussed on their role during development and disease. Analysis of progenitor numbers using fluorescence-activated sorting techniques has resulted in wide-ranging estimates, which may be the result of context-dependent expression of cell surface markers. We have used a colony-forming assay to reliably determine chondroprogenitor numbers in normal and osteoarthritic cartilage where we observed a 2-fold increase in diseased tissue (P < 0.0001). Intriguingly, cell kinetic analysis of clonal isolates derived from single and multiple donors of osteoarthritic cartilage revealed the presence of a divergent progenitor subpopulation characterised by an early senescent phenotype. Divergent sub-populations displayed increased senescence-associated β–galactosidase activity, lower average telomere lengths but retained the capacity to undergo multi-lineage differentiation. Osteoarthritis is an age-related disease and cellular senescence is predicted to be a significant component of the pathological process. This study shows that although early senescence is an inherent property of a subset of activated progenitors, there is also a pool of progenitors with extended viability and regenerative potential residing within osteoarthritic cartilage.

Progenitor cells from different zones of human cartilage and their correlation with histopathological osteoarthritis progression

“…A few prior studies used manual counting methods to measure P CTP‐C and [CTP‐C]. In these reports, P CTP‐C was between 0.1% and 0.2%, or 1,000 and 2,000 progenitors/million cells plated, consistent with our mean of 1,300 CTP‐Cs per million cells. Based on stem cell marker expression, Grogan et al have demonstrated that in comparison to normal cartilage, progenitor cells decrease in non‐fibrillated OA superficial zone and increase in fibrillated OA superficial zone.…”

Progenitor Cells Activated by Platelet Lysate in Human Articular Cartilage as a Tool for Future Cartilage Engineering and Reparative Strategies

“…Previous studies reported that CPC frequency and proliferation increase in pathological cartilage [34,35], but they are not influenced by donor age [34,36].…”

Multi‐Disciplinary Approaches for Cell‐Based Cartilage Regeneration

“…1). 15,17 These cells have been established as not only clonable but also able to differentiate into chondrocytes with the stable cartilage phenotype, [14][15][16][17][18][19][20] which makes them a potentially superior cell type to use for therapies such as those suggested by Brunger et al 11 However, we have also found clones that will consistently undergo endochondral chondrogenesis. 14 In a recent study, we tested human ACP clones from multiple biological replicates for their chondrogenicity in pellet culture at physioxia (defined as 2-5% oxygen for human articular cartilage) and hyperoxia (20% oxygen).…”

“…In a recent study, we tested human ACP clones from multiple biological replicates for their chondrogenicity in pellet culture at physioxia (defined as 2–5% oxygen for human articular cartilage) and hyperoxia (20% oxygen) . As reported by Archer's group, the majority of clones appeared to make cartilage of a stable phenotype, expressing hypertrophic markers (COLXA1, MMP13) only at or below the level of detection. Physioxia decreased any detectable hypertrophic markers even further .…”

“…) . These cells have been established as not only clonable but also able to differentiate into chondrocytes with the stable cartilage phenotype, which makes them a potentially superior cell type to use for therapies such as those suggested by Brunger et al…”