Purpose: Effectiveness of cartilage regenerative approaches are limited by the need to recruit and/or retain repair cells with the ability to form new cartilage tissue at the injury site. This study examines the chemotactic response of articular cartilage Superficial Zone cells to factors that might be used to bring chondroprogenitors to the transplant site, and/or to retain them on scaffolds or other delivery platforms.
Materials & Methods: A 3D hydrogel system was used to study chemotaxis by bovine Superficial Zone chondrocytes in response to stable gradients of an EGFR (Epidermal Growth Factor Receptor) ligand or an inflammatory chemokine, SDF-1α. Parameters of cell migration were quantified by time-lapse imaging in a novel chemotaxis assay system (iBidi) that recapitulates the unique requirements of slow-moving mesenchymal cells for stable, shallow chemotaxis gradients, and a 3-D matrix for adhesion-based movement.
Results: Directed cell movement and overall efficiency of migration (Forward Migration Index) by articular cartilage Superficial Zone cells were optimal at the lowest concentration of EGFR ligand compared to SDF-1α. Chondroprogenitor velocity was increased in a dose dependent fashion with the highest concentrations of both factors revealing a chemokinetic (random movement) effect.
Conclusion: The kinetics of Superficial Zone chondrocyte chemotaxis through a physiologically relevant 3D matrix is consistent with the adhesion-dependent slow migration behavior characteristic of mesenchymal cells. Superficial Zone chondrocytes are extremely sensitive to chemotactic signals provided by EGFR ligand. We suggest this property could be leveraged to encourage recruitment or retention of chondroprogenitor cells at sites of cartilage injury/repair.