Building and regenerating intestines by manipulating intestinal stem cells

Perturbations of the multifaceted functions of the human intestine can manifest in an extraordinarily diverse range of disease pathologies that span developmental, infectious, inflammatory and neoplastic conditions. Accordingly, there is substantial interest in treating intestinal disorders by harnessing the promise of intestinal stem cells (ISCs). From 2009 to 2024, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a multi-institution collaborative, the Intestinal Stem Cell Consortium (ISCC), that sought to leverage advances in ISC biology for clinical translation to accelerate in vivo mucosal repair and eventually generate functioning intestinal tissue ex vivo. In this Roadmap, ISCC members summarize the latest advances and current knowledge gaps both from within the ISCC working group and across the field as a whole as relevant to understanding the human ISC niche, stem cell interactions with and in response to pathogens, and cellular and humoral regenerative strategies, towards realizing stem cell-based therapy for intestinal diseases.