Pluripotent stem cell derived intestinal organoids with an enteric nervous system

Area of Science:

• Stem cell biology
• Developmental biology
• Neuroscience

Background:

• Human pluripotent stem cells (hPSCs) offer a promising source for generating specific human tissues.
• Previous methods allowed for the creation of intestinal organoids but lacked a fully developed enteric nervous system.

Purpose of the Study:

• To generate innervated human intestinal organoids from hPSCs.
• To create a model system for studying enteric nervous system development and diseases.

Main Methods:

• Step-wise differentiation of hPSCs into intestinal organoids.
• Generation of vagal neural crest cells from hPSCs.
• Combination of intestinal organoids and neural crest cells to form innervated organoids.

Main Results:

• Successfully generated three-dimensional innervated human intestinal organoids.
• Organoids exhibited epithelium, neurons, glial cells, and mesenchyme.
• Innervated organoids developed complex structures mirroring the developing human intestine.
• The system demonstrated similar cellular differentiation and organization to the developing intestine.

Conclusions:

• Innervated human intestinal organoids derived from hPSCs represent a significant advancement in regenerative medicine.
• This model system provides novel opportunities for investigating the development and pathophysiology of enteric neuropathies.
• The study highlights technical considerations, advantages, and limitations for generating these complex organoids.