Neural Crest Cell Implantation Restores Enteric Nervous System Function and Alters the Gastrointestinal Transcriptome in Human Tissue-Engineered Small Intestine

Christopher R. Schlieve; Kathryn L. Fowler; Matthew Thornton; Sha Huang; Ibrahim Hajjali; Xiaogang Hou; Brendan Grubbs; Jason R. Spence; Tracy C. Grikscheit

doi:10.1016/j.stemcr.2017.07.017

Stem Cell Reports (Sep 2017)

Neural Crest Cell Implantation Restores Enteric Nervous System Function and Alters the Gastrointestinal Transcriptome in Human Tissue-Engineered Small Intestine

Christopher R. Schlieve,
Kathryn L. Fowler,
Matthew Thornton,
Sha Huang,
Ibrahim Hajjali,
Xiaogang Hou,
Brendan Grubbs,
Jason R. Spence,
Tracy C. Grikscheit

Affiliations

Christopher R. Schlieve: Developmental Biology and Regenerative Medicine Program, The Saban Research Institute at Children's Hospital Los Angeles, 4650 W. Sunset Boulevard, MS#100, Los Angeles, CA 90027, USA
Kathryn L. Fowler: Developmental Biology and Regenerative Medicine Program, The Saban Research Institute at Children's Hospital Los Angeles, 4650 W. Sunset Boulevard, MS#100, Los Angeles, CA 90027, USA
Matthew Thornton: Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, 90033, USA
Sha Huang: Department of Internal Medicine, Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA
Ibrahim Hajjali: Developmental Biology and Regenerative Medicine Program, The Saban Research Institute at Children's Hospital Los Angeles, 4650 W. Sunset Boulevard, MS#100, Los Angeles, CA 90027, USA
Xiaogang Hou: Developmental Biology and Regenerative Medicine Program, The Saban Research Institute at Children's Hospital Los Angeles, 4650 W. Sunset Boulevard, MS#100, Los Angeles, CA 90027, USA
Brendan Grubbs: Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, 90033, USA
Jason R. Spence: Department of Internal Medicine, Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA
Tracy C. Grikscheit: Developmental Biology and Regenerative Medicine Program, The Saban Research Institute at Children's Hospital Los Angeles, 4650 W. Sunset Boulevard, MS#100, Los Angeles, CA 90027, USA

DOI: https://doi.org/10.1016/j.stemcr.2017.07.017
Journal volume & issue: Vol. 9, no. 3
pp. 883 – 896

Abstract

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Acquired or congenital disruption in enteric nervous system (ENS) development or function can lead to significant mechanical dysmotility. ENS restoration through cellular transplantation may provide a cure for enteric neuropathies. We have previously generated human pluripotent stem cell (hPSC)-derived tissue-engineered small intestine (TESI) from human intestinal organoids (HIOs). However, HIO-TESI fails to develop an ENS. The purpose of our study is to restore ENS components derived exclusively from hPSCs in HIO-TESI. hPSC-derived enteric neural crest cell (ENCC) supplementation of HIO-TESI establishes submucosal and myenteric ganglia, repopulates various subclasses of neurons, and restores neuroepithelial connections and neuron-dependent contractility and relaxation in ENCC-HIO-TESI. RNA sequencing identified differentially expressed genes involved in neurogenesis, gliogenesis, gastrointestinal tract development, and differentiated epithelial cell types when ENS elements are restored during in vivo development of HIO-TESI. Our findings validate an effective approach to restoring hPSC-derived ENS components in HIO-TESI and may implicate their potential for the treatment of enteric neuropathies.

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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