The laboratory of James Wells PhD at Cincinnati Children's Hospital has reported a method for the generation of complex, three dimensional intestinal tissues (human intestinal organoids; HIOs) in vitro through directed differentiation of human pluripotent stem cells. These tissues consist of an epithelial layers surrounded by a mesenchyme, contain all major intestinal cell types including absorptive enterocytes and the three secretory lineages (goblet cells, enterendocrine cells, and paneth cells), crypt-like proliferative zones that express intestinal stem cell markers, and exhibit structural/ultrastructural and functional properties of in vivo human intestine. Furthermore, HIOs can be transplanted into immunodeficient mice, wherein they adopt adult intestinal-like tissue architecture and undergo significant maturation. Coupled with our ability to modify gene expression in hPSCs, HIOs represent a highly tractable in vitro system that allows for genetic and/or exogenous environment manipulation to study human intestine development, homeostasis, and disease.
• The PSCF now offers HIO generation as a service.
• Training in HIO generation is also available.
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How can I use HIOs in my research?
Generation of induced pluripotent stem cells from patients with genetic intestinal diseases combined with the differentiation of these cells into HIOs provides a powerful new platform for patient and disease-specific studies of the mechanisms that underlie disease pathogenesis. Furthermore, human embryonic stem cells are amenable to genetic modification using viral vectors or CRISPR/TALEN technologies, making possible the generation of isogenic pluripotent stem cells that can be differentiated into HIOs in vitro. Collectively, these technologies can be used for studies ranging from the genetic basis of the earliest stages of human intestinal development, to the role of specific genes in the phenotypes of intestinal diseases, to the impact of intestinal pathogens on human intestinal biology.