Date of Award

January 2018

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Lawrence Rizzolo

Abstract

Successful differentiation of pluripotent stem cells into retinal cells and subsequent transplantation in animal models have made stem cell-based therapy a closer possibility for treating retinal degenerations. However, major limitations are low efficiency in deriving desired cell types and continued need for large animal studies to validate small animal studies. In this study, we modified a biopolymer scaffold with laminin-521 as a novel substrate to culture retinal progenitor cells (RPCs). We hypothesize that laminin-521 will increase cell retention and provide a developmental signal for RPCs to mature and self-organize. The RPC scaffold culture was transplanted into a RD10 mice, a rodent model of retinal degeneration to evaluate the effects on disease pathology, and into pig eyes for a large animal pilot transplantation study. Differentiation of RPC was monitored by qRT-PCR, immunofluorescence and immunoblotting. Graft survival, integration, and host immune reactivity was assessed via histology and immunofluorescence. The laminin-521 coated scaffold (GCH-L521) increased cell attachment compared to non-coated scaffold. GCH-L521 was able to support growth and continued differentiation of RPC. When transplanted into animal models, the RPC scaffold graft survived in the host and did not cause significant host immune reaction. In RD10 mice, transplantation resulted in improved photoreceptor preservation. GCH-L521 can serve as a new substrate to culture RPC and simultaneously functions as a transplantation vehicle that is well-tolerated in the host.

Comments

This is an Open Access Thesis.

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