Extensive monolayer formation depends on a subpopulation of transplanted human iPSC-derived RPE cells
Tessmer, K.; Gasparini, S. J.; Schmidtke, K.; Adhikari, T.; Michalke, L.; Hammer, J.; Loureiro, L.; Last, A.; Chelius, N.; Kurtz, A.; Johannsen, H.; Carido, M.; Ferguson, S.; Petzold, A.; Friedrich, U. A.; Kurth, T.; Dahl, A.; Feldmann, A.; Almedawar, S.; Knoebel, S.; Ader, M.
Show abstract
Loss of retinal pigment epithelium (RPE) cells in the eye leads to photoreceptor death and vision loss. Cell replacement strategies using RPE derived in vitro from pluripotent stem cells (PSCs) has emerged as a promising therapeutic strategy. Generation of polarized monolayers represents an essential prerequisite for proper RPE function, however, monolayer formation following transplantation of RPE cell suspensions has not been systematically assessed. Using the sodium iodate mouse model of RPE depletion, significant increase in monolayer formation capacity of passage (P) 1 vs. P2 human iPSC-derived RPE cells was observed three weeks after transplantation. Transplant-derived monolayers showed characteristic apicobasal polarity, RPE marker expression, phagocytosis function, and preservation of the host outer nuclear layer. The cell surface marker panel CD54+/PSA-NCAM- was identified to enrich for an RPE subpopulation with high potential for monolayer formation following transplantation. Results underline the importance of defining and isolating competent cell subpopulations for successful RPE transplantation.
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