Progenitor cells from healthy and Osteoarthritic human cartilage show potential for one-stage repair treatment

Abstract

Purpose: This study aims to isolate and characterize articular cartilage-derived progenitor cells (ACPCs) from human cartilage. ACPCs from healthy and osteoarthritic cartilage were compared. In addition, the potential to use these ACPCs in addition to primary chondrocytes for one-stage procedures to treat cartilage defects is assessed. Methods: Cells were isolated from full-thickness healthy (n=6, age 46-49, mean age 48) and osteoarthritic (n=6, age 41-82, mean age 62) human cartilage. Subsequently, ACPCs were isolated from the total cell population by clonal growth after a differential fibronectin adhesion assay. Mesenchymal stromal cells (MSCs) were isolated from human bone marrow. Healthy and osteoarthritic ACPCs were characterized and compared to MSCs by multilineage differentiation and flow cytometry analysis to assess cell surface marker expression. Full-depth chondrocytes of the same donors were assessed as well. Next, ACPCs were cocultured with osteoarthritic chondrocytes in 3D pellet cultures and compared to cocultures of MSCs and chondrocytes. Pellets were harvested after 28 days and assessed for cartilage-like matrix production using quantitative biochemical analyses for glycosaminoglycans and collagen. (Immuno)histochemistry was performed to visualize proteoglycan and collagen production. Results: Healthy and osteoarthritic ACPCs were successfully isolated and differentiated into the adipogenic and chondrogenic lineage (Figure 1), but failed to produce calcified matrix when exposed to osteogenic induction media. Full-depth chondrocytes derived from the same donors were able to produce calcified matrix upon induction of osteogenic differentiation. Both ACPC populations met the criteria for cell surface marker expression to identify mesenchymal stromal cells (MSCs) as determined by flow cytometry. Cartilage-like matrix production was observed in ACPC pellet cultures, as well as pellets consisting of a coculture of ACPCs and chondrocytes. Conclusions: In conclusion, this study provides further insight into a progenitor cell population which is present in both healthy and osteoarthritic human articular cartilage. These populations show similarities to MSCs. Furthermore, ACPCs show potential for use complementary to osteoarthritic chondrocytes in one-stage cartilage repair treatments, as a potential alternative to MSCs.