The conversion of primed pluripotent stem cells to a naive-like state has emerged as a critical strategy for enhancing developmental potential and broadening applications in regenerative medicine. Conditioned media (CM)-based approaches provide a supportive microenvironment enriched with secreted factors that may facilitate this state transition without extensive genetic or chemical manipulation. In this study, we investigated the potential of human Wharton’s Jelly-derived mesenchymal stem cell-conditioned media (hWJ-MSCs-CM) and mouse embryonic fibroblasts CM (MEFs-CM) to support the conversion of primed rhesus monkey embryonic stem cells (rhESCs) into a naive-like state. The rhESCs were cultured under feeder-free and feeder conditions using both hWJ-MSCs-CM and MEFs-CM, exhibiting distinct morphological changes during conversion. Immunofluorescence analysis demonstrated the expression of pluripotency and naive markers under both conditions. Gene expression analysis further confirmed the upregulation of naive-specific genes and downregulation of primed markers, with statistically significant differences between groups. Additionally, epigenetic reprogramming was assessed, revealing differential effects of the CM sources on the reversion to a naive state. These findings highlight the potential of hWJ-MSCs-CM as a supportive system for naive-like state induction in primate ESCs.

This study aimed to examine the potential of human Wharton’s Jelly-derived mes-enchymal stem cells (hWJ-MSCs) in supporting the conversion of the primed state of rhesus monkey embryonic stem cells (rhESCs) to a naïve-like state. The rhESCs were cultured under feeder-free and feeder conditions using hWJ-MSC-conditioned media (hWJ-MSCs-CM) and mouse embryonic fibroblasts CM (MEFs-CM) exhibited distinct morphological changes during conversion. Immunofluorescence analysis demonstrated the expression of pluripotency and naïve markers under both condi-tions. Gene expression analysis further confirmed the upregulation of naïve-specific genes and downregulation of primed markers, with statistically significant differ-ences between groups. Additionally, epigenetic reprogramming was assessed, re-vealing differential effects of the CM sources on the reversion to a naïve state. These findings highlight the potential of hWJ-MSCs-CM as a supportive system for na-ïve-state induction in primate ESCs.