Center For Technology Commercialization

Directed Differentiation of Human Pluripotent Stem Cells into Intestinal Tissue in Culture

(CHMC Ref. Id: 2010-0405)

Overview:

Using developmental paradigms, we have efficiently directed the differentiation of human embryonic and induced pluripotent stem cells (PSCs) into intestinal tissue in vitro.  At the morphological and molecular level, generation of intestinal tissue in culture occurs in a step-wise manner reminiscent of fetal gut development in vivo, culminating in the formation of 3 dimensional gut-like organoids.  Gut organoids undergo morphologic and molecular differentiation into a polarized, columnar intestinal epithelium with a SOX9 positive proliferative zone and villus-like structures that contain the functional cell types of the intestine.  The epithelium is surrounded by mesenchyme that differentiates into smooth muscle cells.  We demonstrate that NEUROG3, a pro-endocrine transcription factor mutated in enteric anendocrinosis, is sufficient to promote differentiation of intestinal epithelial cells towards the enteroendocrine cell lineage.  In conclusion, the ability to generate intestinal tissue from human PSCs in vitro allows for unprecedented studies of human gut development, disease and homeostasis. 

Applications:

• Drug testing
• Tissue regeneration

Advantages:

• Use of induced pluripotent stem cells (PSCs) for differentiation into intestinal tissue in vitro

• Patent Applications Pending

Cincinnati Children's Lead Inventor:

James Wells, Ph.D.