Purpose:
Cell-based therapies for the regeneration of hyaline-like cartilage predominantly involve the use of chondrocytes and mesenchymal stem cells. However, the repair response is impeded by the nature of regenerated tissue, which comprises a mixture of hyaline and fibrocartilage, thus resulting in suboptimal long-term functional outcomes. Current preclinical research demonstrates that cartilage-derived chondroprogenitors display inherent potential for chondrogenesis and appear to be a viable option for cartilage regeneration. Isolation of these progenitors commonly employs the subjection of chondrocytes to fibronectin adhesion assay or strategic use of cartilage explants to obtain chondroprogenitors based on their migratory potential. Although both types of progenitor cells possess characteristics conducive to neocartilage formation, they are isolated using different protocols. A direct comparison between the two cell-types would provide valuable information on the better-suited contender for cartilage repair. The study aimed to compare human migratory and fibronectin adhesion assay-derived chondroprogenitors; to evaluate differences in their biological characteristics and repair potential.
Methods:
Chondroprogenitors were obtained from three human-osteoarthritic knee joints using either explant cultures to obtain migratory chondroprogenitors(MCP) or fibronectin adhesion assay(FAA-CP). Assessment parameters included immunophenotyping, growth kinetics, multilineage differentiation potential with particular attention to assessing chondrogenic potential using mRNA expression for markers of chondrogenesis and hypertrophy, GAG/DNA, and histological staining under normoxia and hypoxia culture conditions.
Results:
Normoxia and hypoxia MCPs displayed significantly lower levels of the hypertrophy marker RUNX2 and fibrocartilage marker COL1A1 compared to the FAA counterparts. Concerning their chondrogenic potential, normoxia-MCPs exhibited significantly higher levels of the chondrogenic gene Aggrecan and COL2A1/COL1A1 ratio. Additionally, normoxia-MCPs displayed efficient histological staining and total GAG/DNA, reiterating its better chondrogenic potential.
Conclusion:
Normoxia-MCPs displayed superior regenerative potential for cartilage repair, owing to their higher chondrogenic and limited hypertrophic ability. Focused investigations to study its regenerative potential using in-vivo models are warranted to understand its therapeutic potential.