High-throughput screening for directed chemotaxis of retinal progenitor cells in 3D hydrogels

This study utilizes high-throughput screening to examine human retinal progenitor cell migration in response to biomaterial and chemokine stimuli. Degenerative diseases of the retina impact millions of people worldwide each year, with no known cure available to date. Implantation of retinal progenitor cells in animal models has shown considerable promise but is limited by extremely low (<;5%) levels of integration. We hypothesize that by providing a supportive biomaterial and optimized chemokine concentrations to the subretinal space, directed migration of implanted progenitors could be achieved, aiding cell survival, integration, and differentiation postimplantation. In this work, a high-throughput screen was applied to examine retinal progenitor cell migration in response to two hydrogel compositions (collagen type I, collagen type I:10% MatrigelTM) and three growth factors implicated in migratory cascades: Epidermal Growth Factor (EGF), Fibroblast Growth Factor-2 (FGF-2), and Stromal Cell Derived Factor-1 (SDF-1). After 48 hours, the addition of EGF at various concentrations increased migration in both hydrogel compositions 1.9-2.6-fold compared to chemokine free controls. FGF-2 increased migration 1.4-2.2-fold in collagen gels, however did not impact migration in MatrigelTM composites. SDF-1 did not impact migration in MatrigelTM composites but increased migration 1.8-3.4-fold in collagen gels with a maximal response at 20 ng/mL. Progenitors penetrate farther in collagen I compared to MatrigelTM composites. These results support the significance of matrix and chemokines to induce migration towards optimizing a rational therapy for retinal degeneration.