Abstract
Regenerative retinal therapies have introduced progenitor cells to replace dysfunctional or injured neurons and regain visual function. While contemporary cell replacement therapies have delivered retinal progenitor cells (RPCs) within customized biomaterials to promote viability and enable transplantation, outcomes have been severely limited by the misdirected and/or insufficient migration of transplanted cells. RPCs must achieve appropriate spatial and functional positioning in host retina, collectively, to restore vision, whereas movement of clustered cells differs substantially from the single cell migration studied in classical chemotaxis models. Defining how RPCs interact with each other, neighboring cell types and surrounding extracellular matrixes are critical to our understanding of retinogenesis and the development of effective, cell-based approaches to retinal replacement. The current article describes a new bio-engineering approach to investigate the migratory responses of innate collections of RPCs upon extracellular substrates by combining microfluidics with the well-established invertebrate model of Drosophila melanogaster. Experiments utilized microfluidics to investigate how the composition, size, and adhesion of RPC clusters on defined extracellular substrates affected migration to exogenous chemotactic signaling. Results demonstrated that retinal cluster size and composition influenced RPC clustering upon extracellular substrates of concanavalin (Con-A), Laminin (LM), and poly-L-lysine (PLL), and that RPC cluster size greatly altered collective migratory responses to signaling from Fibroblast Growth Factor (FGF), a primary chemotactic agent in Drosophila. These results highlight the significance of examining collective cell-biomaterial interactions on bio-substrates of emerging biomaterials to aid directional migration of transplanted cells. Our approach further introduces the benefits of pairing genetically controlled models with experimentally controlled microenvironments to advance cell replacement therapies.
Highlights
Visual centers in the brain are activated when groups of progenitor cells interconnect to establish the highly organized, synaptic structure of neurosensory retina [1,2,3]
This study examined how chemical cues from a controlled signaling microenvironment influenced the independent and collective chemotactic behavior of heterogeneous populations of retinal progenitor cells (RPCs)
All tests were performed using primary RPCs dissected from eye-brain complexes of third instar larvae Drosophila
Summary
Visual centers in the brain are activated when groups of progenitor cells interconnect to establish the highly organized, synaptic structure of neurosensory retina [1,2,3]. Cells 2019, 8, 1301 progenitors must move appropriately to align themselves with neighboring cell groups to establish tissue architecture [5,6]. In retina, both processes rely upon the collective migration of RPCs, i.e., movement of clustered cells as a group rather than as individual cells [3,5,6]. Both processes rely upon the collective migration of RPCs, i.e., movement of clustered cells as a group rather than as individual cells [3,5,6] Such collective movements may differ substantially from the migration of individual cells studied in classical models of chemotaxis (reviewed in [7,8,9,10]), despite the same chemotactic stimuli driving locomotion. Individual cells chemotax independent of cell-cell adhesions, with a typical fibroblast locomotor cycle consisting of cellular protrusions and adhesion to the leading edge, development of contractile forces between the front and trailing edge, and release of trailing adhesions due to the applied tension [11,12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
