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

被引：99

作者：

Schlieve, Christopher R. ^{[1
,2
]}

Fowler, Kathryn L. ^{[1
]}

Thornton, Matthew ^{[3
]}

Huang, Sha ^{[4
,5
,6
]}

Hajjali, Ibrahim ^{[1
]}

Hou, Xiaogang ^{[1
]}

Grubbs, Brendan ^{[3
]}

Spence, Jason R. ^{[4
,5
,6
]}

Grikscheit, Tracy C. ^{[1
,2
]}

机构：

[1] Childrens Hosp Los Angeles, Saban Res Inst, Dev Biol & Regenerat Med Program, 4650 W Sunset Blvd,MS 100, Los Angeles, CA 90027 USA

[2] Childrens Hosp Los Angeles, Dept Surg, Div Pediat Surg, Los Angeles, CA 90027 USA

[3] Univ Southern Calif, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA

[4] Univ Michigan, Sch Med, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA

[5] Univ Michigan, Ctr Organogenesis, Sch Med, Ann Arbor, MI 48109 USA

[6] Univ Michigan, Dept Cell & Dev Biol, Sch Med, Ann Arbor, MI 48109 USA

来源：

STEM CELL REPORTS | 2017年 / 9卷 / 03期

关键词：

PLURIPOTENT STEM-CELLS; NITRIC-OXIDE SYNTHASE; PROGENITOR CELLS; HIRSCHSPRUNG DISEASE; INTERSTITIAL-CELLS; MURINE MODEL; IN-VITRO; GUT; COLON; MOTILITY;

D O I：

10.1016/j.stemcr.2017.07.017

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：883 / 896

页数：14

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