Derivation and Initial Characterization of Retinal Pigment Epithelium from Urine-Derived iPSCs

Age-related macular degeneration (AMD), particularly its dry form, is a leading cause of irreversible vision loss due to retinal pigment epithelium (RPE) dysfunction and loss. Addressing this unmet therapeutic need requires non-invasive strategies for generating patient-specific RPE cells. This study reports the successful generation and initial characterization of RPE cells derived from urine-derived induced pluripotent stem cells (u-iPSC-RPE). Urine-derived stem cells (USCs) were isolated from healthy individuals and comprehensively characterized, confirming strong expression of renal progenitor makers and mesenchymal stem cell markers, while lacking standard hematopoietic markers. USCs were reprogrammed into iPSCs using the integration-free Sendai virus expressing the Yamanaka factors. The reprogrammed u-iPSC clones displayed characteristic pluripotency marker expression and demonstrated clearance of the Sendai virus by later passages. Subsequently, these u-iPSCs were efficiently differentiated into RPE cells, exhibiting characteristic hexagonal morphology and pigmentation which was confirmed by the expression of key RPE-specific proteins. Our findings demonstrated the feasibility of generating patient-specific RPE cells from readily accessible USCs. This reliable method for producing u-iPSC-RPE from urine-derived progenitor cells provides a promising foundation for future studies investigating their functional potential in vitro and their use in in vivo models for retinal disease modeling and therapeutic applications for AMD.