The transition into the naïve state in human pluripotent stem cells (hPSCs) represents a crucial advancement in stem cell biology, as it captures the cells in a more primitive/neutral and epigenetically unrestricted state, therefore offering more plasticity compared to the primed state. Achieving this naïve state is essential for maximizing the potential of hPSCs in regenerative medicine and developmental studies.

Traditionally, Matrigel has been employed as a plate coating for growing hPSCs; however, Matrigel contains animal-derived components that may present transgenic significant limitations for clinical applications. In this study, we explore the efficacy of using a xeno-free plate coating, PMEDSAH, for inducing hPSCs to a naïve state using FINE (Szczerbinska,et.al) and NHSM (Weinberger, et.al, Romayor et.al.) cell culture media. Our findings indicate that PMEDSAH supports robust cell growth and pluripotency with NHSM media, offering a viable alternative to Matrigel. Both media demonstrated effective reversion to the naïve state, characterized by the expression of key naïve pluripotency markers. Our data suggest that NHSM media in PMEDSAH plates seemed to enhance naïve cell induction. This work underscores the importance of adopting xeno-free culture systems and optimized media formulations to advance the clinical and research applications of naïve hPSCs.