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Influence of Substrate Stiffness on iPSC-Derived Retinal Pigmented Epithelial Cells
Journal article   Open access   Peer reviewed

Influence of Substrate Stiffness on iPSC-Derived Retinal Pigmented Epithelial Cells

Rion J Wendland, Budd A Tucker and Kristan S Worthington
Stem cells translational medicine, Vol.13(6), pp.582-592
06/2024
DOI: 10.1093/stcltm/szae022
PMCID: PMC11165161
PMID: 38560893
url
https://doi.org/10.1093/stcltm/szae022View
Published (Version of record) Open Access

Abstract

Retinal degenerative diseases are a major cause of blindness involving the dysfunction of photoreceptors, retinal pigmented epithelium (RPE), or both. A promising treatment approach involves replacing these cells via surgical transplantation, and previous work has shown that cell delivery scaffolds are vital to ensure sufficient cell survival. Thus, identifying scaffold properties that are conducive to cell viability and maturation (such as suitable material and mechanical properties) is critical to ensuring a successful treatment approach. In this study, we investigated the effect of scaffold stiffness on human RPE attachment, survival, and differentiation, comparing immortalized (ARPE-19) and stem cell-derived RPE (iRPE) cells. Polydimethylsiloxane was used as a model polymer substrate, and varying stiffness (~12 to 800 kPa) was achieved by modulating the cross-link-to-base ratio. Post-attachment changes in gene and protein expression were assessed using qPCR and immunocytochemistry. We found that while ARPE-19 and iRPE exhibited significant differences in morphology and expression of RPE markers, substrate stiffness did not have a substantial impact on cell growth or maturation for either cell type. These results highlight the differences in expression between immortalized and iPSC-derived RPE cells, and also suggest that stiffnesses in this range (~12-800 kPa) may not result in significant differences in RPE growth and maturation, an important consideration in scaffold design.
Cell Transplantation Tissue Engineering microenvironment retina retinal pigmented epithelium

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