Format

Send to

Choose Destination
EMBO J. 2015 May 5;34(9):1149-63. doi: 10.15252/embj.201490686. Epub 2015 Mar 19.

Generating human intestinal tissues from pluripotent stem cells to study development and disease.

Author information

1
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
2
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA james.wells@cchmc.org.

Abstract

As one of the largest and most functionally complex organs of the human body, the intestines are primarily responsible for the breakdown and uptake of macromolecules from the lumen and the subsequent excretion of waste from the body. However, the intestine is also an endocrine organ, regulating digestion, metabolism, and feeding behavior. Intricate neuronal, lymphatic, immune, and vascular systems are integrated into the intestine and are required for its digestive and endocrine functions. In addition, the gut houses an extensive population of microbes that play roles in digestion, global metabolism, barrier function, and host-parasite interactions. With such an extensive array of cell types working and performing in one essential organ, derivation of functional intestinal tissues from human pluripotent stem cells (PSCs) represents a significant challenge. Here we will discuss the intricate developmental processes and cell types that are required for assembly of this highly complex organ and how embryonic processes, particularly morphogenesis, have been harnessed to direct differentiation of PSCs into 3-dimensional human intestinal organoids (HIOs) in vitro. We will further describe current uses of HIOs in development and disease research and how additional tissue complexity might be engineered into HIOs for better functionality and disease modeling.

KEYWORDS:

endoderm; intestinal development; organoids; stem cells; tissue engineering

PMID:
25792515
PMCID:
PMC4426477
DOI:
10.15252/embj.201490686
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center