Engineering a second brain in a dish.

The utilization of human pluripotent stem cells holds great promise in elucidating principles of developmental biology and applications in personalized and regenerative medicine. Breakthroughs from the last decade have allowed the scientific community to better understand and successfully manipulate human pluripotent stem cells using distinct differentiation strategies into a variety of target tissues. This manipulation relies solely on our understanding of developmental processes occurring in model organisms. The in vitro translation of our developmental knowledge upon stem cells provides a new means to generate specific tissue to understand developmental and disease mechanisms, as well as physiological processes. The generation of an integrated human intestinal tissue is one such example. In this review, we highlight the biological motivation behind the generation of human intestinal organoids. We further describe the integration of an enteric nervous system within the organoid to generate a functional intestine. Forthcoming strategies to add additional complexities to the intestinal tissue so as to better understand how our "second brain" functions within the gut are also discussed. The organoid system offers a promising avenue to understand how the enteric nervous system works and patterns the human intestine during both physiology and disease.