Article1 min read·Published Oct 2014Older

An in vivo model of human small intestine using pluripotent stem cells

Part of Intestinal Organoid Science & Bioengineering 49 items

pubmed.ncbi.nlm.nih.gov

Michael Helmrath

Differentiation of human pluripotent stem cells (hPSCs) into organ-specific subtypes offers an exciting avenue for the study of embryonic development and disease processes, for pharmacologic studies and as a potential resource for therapeutic transplant. To date, limited in vivo models exist for human intestine, all of which are dependent upon primary epithelial cultures or digested tissue from surgical biopsies that include mesenchymal cells transplanted on biodegradable scaffolds. Here, we generated human intestinal organoids (HIOs) produced in vitro from human embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) that can engraft in vivo. These HIOs form mature human intestinal epithelium with intestinal stem cells contributing to the crypt-villus architecture and a laminated human mesenchyme, both supported by mouse vasculature ingrowth. In vivo transplantation resulted in marked expansion and maturation of the epithelium and mesenchyme, as demonstrated by differentiated intestinal cell lineages (enterocytes, goblet cells, Paneth cells, tuft cells and enteroendocrine cells), presence of functional brush-border enzymes (lactase, sucrase-isomaltase and dipeptidyl peptidase 4) and visible subepithelial and smooth muscle layers when compared with HIOs in vitro. Transplanted intestinal tissues demonstrated digestive functions as shown by permeability and peptide uptake studies. Furthermore, transplanted HIO-derived tissue was responsive to systemic signals from

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Article · Oct 2014 · 1 min read

In brief

Researchers successfully generated functional human intestinal tissue from pluripotent stem cells and transplanted it into animal models, where it matured into complex intestinal architecture with all major cell types and digestive functions. This approach offers a novel platform for studying intestinal development, disease modeling, and potential therapeutic applications without requiring primary tissue biopsies.

Written by the GCMD Library team from the article.

Michael Helmrath

Statements in this article

Human intestinal organoids can be generated in vitro from human embryonic stem cells or induced pluripotent stem cells and successfully engrafted in vivo.
Research
Transplanted human intestinal organoids form mature human intestinal epithelium with intestinal stem cells contributing to crypt-villus architecture and a laminated human mesenchyme supported by mouse vasculature ingrowth.
Research
In vivo transplantation results in marked expansion and maturation of the epithelium and mesenchyme compared with human intestinal organoids maintained in vitro.
Research
Transplanted human intestinal organoids demonstrate differentiated intestinal cell lineages including enterocytes, goblet cells, Paneth cells, tuft cells and enteroendocrine cells.
Research
Transplanted human intestinal organoids express functional brush-border enzymes including lactase, sucrase-isomaltase and dipeptidyl peptidase 4.
Research
Transplanted human intestinal organoids develop visible subepithelial and smooth muscle layers.
Research
Transplanted human intestinal organoid-derived tissue demonstrates digestive functions as shown by permeability and peptide uptake studies.
Research
Transplanted human intestinal organoid-derived tissue is responsive to systemic signals.
Research