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Cited by 626

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system

Open access
Workman, Michael J, Mahe, Maxime M, Trisno, Stephen, Poling, Holly M, Watson, Carey L, Sundaram, Nambirajan, Chang, Ching-Fang, Schiesser, Jacqueline, Aubert, Philippe, Stanley, Edouard G, Elefanty, Andrew G, Miyaoka, Yuichiro, Mandegar, Mohammad A, Conklin, Bruce R, Neunlist, Michel, Brugmann, Samantha A, Helmrath, Michael A, Wells, James M·2017·Nature Medicine
DOI 10.1038/nm.4233
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Abstract

The enteric nervous system (ENS) of the gastrointestinal tract controls many diverse functions, including motility and epithelial permeability. Perturbations in ENS development or function are common, yet there is no human model for studying ENS-intestinal biology and disease. We used a tissue-engineering approach with embryonic and induced pluripotent stem cells (PSCs) to generate human intestinal tissue containing a functional ENS. We recapitulated normal intestinal ENS development by combining human-PSC-derived neural crest cells (NCCs) and developing human intestinal organoids (HIOs). NCCs recombined with HIOs in vitro migrated into the mesenchyme, differentiated into neurons and glial cells and showed neuronal activity, as measured by rhythmic waves of calcium transients. ENS-containing HIOs grown in vivo formed neuroglial structures similar to a myenteric and submucosal plexus, had functional interstitial cells of Cajal and had an electromechanical coupling that regulated waves of propagating contraction. Finally, we used this system to investigate the cellular and molecular basis for Hirschsprung's disease caused by a mutation in the gene PHOX2B. This is, to the best of our knowledge, the first demonstration of human-PSC-derived intestinal tissue with a functional ENS and how this system can be used to study motility disorders of the human gastrointestinal tract.

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Metadata

Authors
Workman, M. J., Mahe, M. M., Trisno, S., Poling, H. M., Watson, C. L., Sundaram, N., Chang, C.-F., Schiesser, J., Aubert, P., Stanley, E. G., Elefanty, A. G., Miyaoka, Y., Mandegar, M. A., Conklin, B. R., Neunlist, M., Brugmann, S. A., Helmrath, M. A., & Wells, J. M.
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2016-11-21
Volume
23
Issue
1
Pages
49-59
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/nm.4233
OpenAlex
W2549963625
Cited by
626
References
6
FWCI
51.11
Type
journal article
Language
en
Open access
green

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