The combination of dibenzazepine and a DOT1L inhibitor enables a stable maintenance of human naïve-state pluripotency in non-hypoxic conditions

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Conventional human pluripotent stem cells (hPSCs), known for being in a primed state, are pivotal for both basic research and clinical applications since such cells produce various types of differentiated cells. Recent reports on PSCs shed light on the pluripotent hierarchy of stem cells and have promoted the exploration of new stem cell states along with their culture systems. Human naïve PSCs are expected to provide further knowledge of early developmental mechanisms and improvements for differentiation programmes in the regenerative therapy of conventionally primed PSCs. However, practical challenges exist in using naïve-state PSCs such as determining the conditions for hypoxic culture condition and showing limited stable cellular proliferation. Here, we have developed new leukemia inhibitory factor dependent PSCs by applying our previous work, the combination of dibenzazepine and a DOT1L inhibitor to achieve the stable culture of naïve-state PSCs. The potential of these cells to differentiate into all three germ layers was shown both in vitro and in vivo . Such new naïve-state PSCs formed dome-shaped colonies at a faster rate than conventional, primed-state human induced PSCs and could be maintained for an extended period in the absence of hypoxic culture conditions. We also identified relatively high expression levels of naïve cell markers. Thus, non-hypoxia treated, leuke

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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