Organoid Maturation by Circadian Entrainment

Stem cell-derived tissues that recap endogenous physiology are key for regenerative medicine. Yet, most methods yield products that function like fetal, not adult tissues. Organoids are typically grown in constant environments, while our tissues mature along with behavioral cycles. Here, we show that inducing circadian rhythms in pancreatic islet organoids, by entraining them to daily feeding-fasting cycles, elicits their metabolic maturation. Our results show that rhythms can be harnessed to further functional maturation of organoids destined for human therapeutics.