Journal article
Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system
MJ Workman, MM Mahe, S Trisno, HM Poling, CL Watson, N Sundaram, CF Chang, J Schiesser, P Aubert, EG Stanley, AG Elefanty, Y Miyaoka, MA Mandegar, BR Conklin, M Neunlist, SA Brugmann, MA Helmrath, JM Wells
Nature Medicine | NATURE PUBLISHING GROUP | Published : 2017
DOI: 10.1038/nm.4233
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 c..
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Awarded by National Institute of Diabetes and Digestive and Kidney Diseases
Funding Acknowledgements
We thank A. Zorn, N. Shroyer and members of the Wells and Zorn laboratories for reagents and feedback. We thank M. Kofron for assistance with confocal imaging. We thank S. Danzer, R. Pun, J. Piero, M. Marotta and M. Oria for help with the equipment for the electrical field stimulation experiments. We thank K. Campbell and J. Kuerbitz for providing antibodies for the neurochemical analysis. This work was supported by US National Institutes of Health grants U18TR000546 (J.M.W.), U18EB021780 (J.M.W. and M.A.H.), U01DK103117 (J.M.W. and M.A.H.), R0IDK098350 (J.M.W.) and R01DK092456 (J.M.W.), and an Athena Blackburn Research Scholar Award in Neuroenteric Diseases (M.M.M.). We also acknowledge core support from the Cincinnati Digestive Disease Center Award (P30 DK0789392; Pilot and Feasibility Award), Clinical Translational Science Award (U54 RR025216) and technical support from Cincinnati Children's Hospital Medical Center (CCHMC) Confocal Imaging Core and the CCHMC human Pluripotent Stem Cell Facility.