Effective surgical treatment of meniscus injuries has been a challenge for decades. Stimulating meniscus regeneration through transplantation of meniscal progenitor cells has been proposed as a promising new strategy. The purpose of this study was to comprehensively phenotype regional progenitor populations in the human meniscus and donor-matched articular cartilage.
Progenitor populations were isolated by selective adhesion to fibronectin from avascular and vascular regions of menisci and articular cartilage (n=5) harvested from human arthroplasty donors, as well as donor-matched whole mixed populations (no selective adhesion to fibronectin) for comparison. Growth kinetics and immunoprofiling were assessed at passage 0, and gene expression analysis and 3D pellet chondrogenic capacity were assessed at passage 2 for the different cell populations.
Fibronectin-selection resulted in populations resembling progenitors from the avascular and vascular menisci (PAvas and PVas, respectively) and also articular cartilage (PChs); these all demonstrated colony forming capacity on monolayer culture, whereas their mixed populations did not. PVas had a significant lower population doubling time cf. their vascular mixed counterparts. PVas also proliferated significantly faster than PAvas and PChs. Each progenitor cell population were significantly more immunopositivite for CD49b and CD49c cf. their mixed populations and PChs had a higher positivity level of CD166 compare to mixed chondrocytes. Collagen type I was upregulated and type II downregulated in progenitor pellets cf. mixed pellets. GAG/DNA analysis demonstrated that progenitor cells produced more GAGs per cell than mixed populations in all regions.
Our study demonstrates that the human meniscus contains meniscal progenitor populations that retain colony forming capacity and have a distinct immunoprofile and matrix forming capacity in both the avascular and vascular regions. The findings of this study build on the body of evidence which suggests that meniscal progenitors represent attractive novel cell therapy populations for the enhancement of meniscal regeneration.