Induced Pluripotent Stem Cell-Derived Human Intestinal Organoids Accurately Model Gut Function

Study in a Sentence: Researchers at Boston University developed a directed differentiation protocol to produce induced pluripotent stem cells (iPSC)-derived mesenchyme-free human intestinal organoids (HIOs) and used them to create cystic fibrosis patient-derived iPSC-derived organoids for the study of disease-causing mechanisms.

Healthy for Humans: The ability to generate iPSC-derived HIOs in an efficient manner enables in vitro studies of healthy and disease states of the gut that more closely resemble human in vivo function than 2D and animal systems and eliminate the need for invasive procedures to obtain intestinal and colonic biopsy samples. With this system, a variety of diseases, such as cystic fibrosis or inflammatory bowel disease, can be modeled for mechanistic understanding and therapeutic screening applications.

Redefining Research: Previous iPSC-derived HIO protocols generated organoids with both epithelial and mesenchymal cells, deviating from in vivo intestinal tissue characteristics and requiring an additional sorting step in order to isolate epithelial-specific cell populations. Researchers modified this protocol to use a well-defined, serum-free media for the generation of mesenchyme-free HIOs, increasing protocol efficiency and reducing the experimental noise associated with a mesenchyme-containing system.