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Human Retinal Progenitor Cell (hRPC) Migration in Three-Dimensional (3D) Environments of Varying Stiffness and
Peng Zhao1, Joydip Kundu1, Douglas Blanton1
1Department of Chemical Engineering, Northeastern University, Boston, Massachusetts, USA.
Journal of Tissue Engineering and Regenerative Medicine
|November 6, 2025
Summary
Optimizing biomaterial stiffness and incorporating stromal cell-derived factor (SDF) and hepatocyte growth factor (HGF) can enhance human retinal progenitor cell (hRPC) migration for vision restoration therapies.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Ophthalmology
Background:
- Retinal degeneration is a primary cause of global blindness.
- Subretinal implantation of human retinal progenitor cells (hRPCs) shows potential for vision restoration but suffers from poor cell integration (<2%).
- Effective integration hinges on implanted cell migration within the degenerating retina, influenced by the biomaterial microenvironment.
Purpose of the Study:
- To identify cues within biomaterial carriers that promote hRPC migration.
- To investigate the role of material properties (composition, stiffness) and soluble factors in hRPC migration.
- To elucidate the signaling pathways involved in hRPC migration.
Main Methods:
- Developed 3D hydrogel matrices (collagen type I, collagen type I methacrylate, hyaluronic acid glycidyl methacrylate) with varying stiffness.
- Assessed hRPC migration in response to different hydrogel compositions and stiffness.
- Evaluated the effect of growth factors (EGF, FGF, SDF, HGF) on hRPC migration within collagen gels.
- Identified signaling pathways (Akt, MAPK) correlated with migration using multiplex ELISA and PLSR modeling.
Main Results:
- hRPC migration varied significantly with hydrogel composition and stiffness; higher migration observed in collagen-based gels with increased component concentration and stiffness.
- Stromal cell-derived factor (SDF) and hepatocyte growth factor (HGF) significantly increased hRPC migration compared to controls.
- Akt and MAPK signaling pathways were identified as key nodes correlating with hRPC migration.
Conclusions:
- Material stiffness and the inclusion of specific soluble factors (SDF, HGF) are critical parameters for designing effective cell delivery vehicles.
- Optimizing biomaterial carriers can enhance transplanted hRPC migration, potentially improving integration and vision restoration outcomes in retinal degeneration.
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