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Elodie Lawley, Petr Baranov, Michael Young; Hybrid vitronectin-mimicking polycaprolactone scaffolds and human retinal progenitor cell composites. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4685.
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Many advances have been made in the development of treatments for retinal degenerative diseases such as age-related macular degeneration and retinitis pigmentosa. The irreversible loss of photoreceptors is common to both and currently, no restorative clinical treatment exists. It has been shown that progenitor cell transplantation can rescue retinal structure and function. This cell type can be collected from the developing neural retina, greatly expanded in vitro, and delivered into the degenerative host as a single-cell suspension or as composite graft. Previously, we have described several polymer scaffolds for culture and transplantation of retinal progenitor cells (RPC). This tissue engineering strategy increases donor cell survival, integration and differentiation. However, it conveys poor adhesive properties limiting its use and therefore requires additional surface modifications.
The aim of this work was to study hybrid vitronectin-mimicking PCL scaffolds and their effects on hRPC adhesion, proliferation, differentiation and integration. In this study, we use Corning Synthemax II-SC as the vitronectin-mimicking substrate which mimics the natural cell environment. In turn, it also enhances expansion to create a clinically relevant number of cells for transplantation and supports differentiation. The differentiation of hRPC on the polymer was assessed by flow cytometry for mature photoreceptor markers, and the effect of the scaffold strategy on the transplantation outcome by the explant approach whereby composite grafts were placed on top of the pig retina.
We were able to successfully incorporate a vitronectin-mimicking adhesive oligopeptide (Synthemax II) into a PCL scaffold and show that the incorporation into PCL leads to dose-dependent increase of cell adhesion, required for efficient hRPC culture. The optimal dose of Synthemax II was 30ug/ml (adhesion increased from 10% to 65%), which was equal to standard fibronectin-coating. Incorporation of the oligopeptide into PCL did not change the inhibitory effect of PCL on hRPC proliferation: the population increase was 1.3 fold after 72 hours in culture.
Hybrid vitronectin-mimicking polycaprolactone polymers can serve as scaffolds for hRPCs, and the composite can be used to evaluate the potency of cells to be used in transplantation studies.
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