Abstract
Gastrointestinal organoids are an exciting new tool for modeling human development, physiology, and disease in human tissue. Derived from pluripotent stem cells, gastrointestinal organoids consist of epithelial and mesenchymal cells organized in an intricate, three-dimensional structure that recapitulates the physiology and microscopic anatomy of the human gastrointestinal (GI) tract. In vitro derivation of gastrointestinal organoids from definitive endoderm has permitted an exploration of the complex signaling pathways required for the initial maturation of each individual gastrointestinal organ. Further maturation beyond an early fetal state currently requires transplantation into an immunocompromised host. Transplantation-induced maturation provides an opportunity to functionally interrogate the key mechanisms underlying development of the human GI tract. Gastrointestinal organoids can also be used to model human diseases and ultimately may serve as the basis for developing novel, personalized therapies for human intestinal diseases.
Highlights
Remarkable insight into the key pathways underlying intestinal development, physiology, and diseases has been obtained using a variety of model organisms [33, 38, 50]
pluripotent stem cells (PSCs)-derived gastrointestinal organoids have proven to be an effective tool for studying the development of the human gastrointestinal tract
In vitro gastrointestinal organoids have been especially useful for delineating the key mechanisms underlying the specification of endoderm into different GI lineages, as well as for exploring the pathways required for the differentiation of specific cell types
Summary
Remarkable insight into the key pathways underlying intestinal development, physiology, and diseases has been obtained using a variety of model organisms [33, 38, 50]. Enteroids cultured in the traditional fashion are excellent tools to address in vitro questions regarding the intestinal epithelium, they lack mesenchymal, neuronal, and immune compartments This can limit their use for studying complex, nonepithelial intestinal physiology and pathology, including diseases such as Hirschsprung disease, which impacts the enteric nervous system, and Berdon syndrome, which impacts the enteric smooth muscle [1, 4]. There is a need to define human intestinal fibroblast populations in tHIOs and to functionally interrogate their roles in intestinal development, physiology, and pathology Another major question raised by transplantation-induced maturation is whether tHIOs can be used to model human fetal intestinal development. Future work will be required to further explore the mechanisms through which strain induces maturation of both the epithelial and mesenchymal compartments, as well as to determine whether these mechanisms can be used to further mature HIOs in vitro
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