Article1 min read·Published Dec 2021Older

Functional human gastrointestinal organoids can be engineered from three primary germ layers derived separately from pluripotent stem cells

Part of Intestinal Organoid Science & Bioengineering 49 items

pubmed.ncbi.nlm.nih.gov

Michael Helmrath

Human organoid model systems lack important cell types that, in the embryo, are incorporated into organ tissues during development. We developed an organoid assembly approach starting with cells from the three primary germ layers-enteric neuroglial, mesenchymal, and epithelial precursors-that were derived separately from human pluripotent stem cells (PSCs). From these three cell types, we generated human antral and fundic gastric tissue containing differentiated glands surrounded by layers of smooth muscle containing functional enteric neurons that controlled contractions of the engineered antral tissue. Using this experimental system, we show that human enteric neural crest cells (ENCCs) promote mesenchyme development and glandular morphogenesis of antral stomach organoids. Moreover, ENCCs can act directly on the foregut to promote a posterior fate, resulting in organoids with a Brunner's gland phenotype. Thus, germ layer components that are derived separately from PSCs can be used for tissue engineering to generate complex human organoids.

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Article · Dec 2021 · 1 min read

In brief

Researchers engineered functional human gastric organoids by separately deriving and assembling cells from all three germ layers using pluripotent stem cells. The resulting tissues contain differentiated glands, smooth muscle, and functional enteric neurons, demonstrating that enteric neural crest cells promote mesenchyme development and can direct foregut fate specification.

Written by the GCMD Library team from the article.

Michael Helmrath

Statements in this article

Human organoid model systems lack important cell types that are incorporated into organ tissues during embryonic development.
Established
Functional human antral and fundic gastric tissue can be generated from three separately derived primary germ layer cell types: enteric neuroglial, mesenchymal, and epithelial precursors from pluripotent stem cells.
Research
Engineered gastric organoids contain differentiated glands surrounded by layers of smooth muscle with functional enteric neurons that control contractions.
Research
Human enteric neural crest cells promote mesenchyme development in antral stomach organoids.
Research
Human enteric neural crest cells promote glandular morphogenesis of antral stomach organoids.
Research
Enteric neural crest cells can act directly on the foregut to promote a posterior fate, resulting in organoids with a Brunner's gland phenotype.
Research
Germ layer components derived separately from pluripotent stem cells can be used for tissue engineering to generate complex human organoids.
Research