Xenotransplantation of human intestine into mouse abdomen or subcutaneous tissue: Novel platforms for the study of the human enteric nervous system

N. Nagy, N. Marsiano, R. S. Bruckner, M. Scharl, M. J. Gutnick, S. Yagel, E. Arciero, A. M. Goldstein, N. Y. Shpigel

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Current efforts to develop stem cell therapy as a novel treatment for neurointestinal diseases are limited by the unavailability of a model system to study cell transplantation in the human intestine. We propose that xenograft models support enteric nervous system (ENS) development in the fetal human intestine when transplanted into mice subcutaneously or intra-abdominally. Methods: Fetal human small and large intestine were grafted onto the small intestinal mesentery and into the subcutaneous tissue of immunodeficient mice for up to 4 months. Intestinal cytoarchitecture and ENS development were studied using immunohistochemistry. Key Results: In both abdominal and subcutaneous grafts, the intestine developed normally with formation of mature epithelial and mesenchymal layers. The ENS was patterned in two ganglionated plexuses containing enteric neurons and glia, including cholinergic and nitrergic neuronal subtypes. c-Kit-immunoreactive interstitial cells of Cajal were present in the gut wall. Conclusions & Inferences: Abdominal xenografts represent a novel model that supports the growth and development of fetal human intestine. This in vivo approach will be a useful method to study maturation of the ENS, the pathophysiology of neurointestinal diseases, and the long-term survival and functional differentiation of neuronal stem cells for the treatment of enteric neuropathies.

Original languageEnglish
Article numbere13212
JournalNeurogastroenterology and Motility
Volume30
Issue number3
DOIs
Publication statusPublished - Mar 1 2018

Fingerprint

Enteric Nervous System
Heterologous Transplantation
Subcutaneous Tissue
Abdomen
Intestines
Heterografts
Stem Cells
Interstitial Cells of Cajal
Intestinal Pseudo-Obstruction
Mesentery
Large Intestine
Cell Transplantation
Cell- and Tissue-Based Therapy
Fetal Development
Growth and Development
Neuroglia
Cholinergic Agents
Small Intestine
Immunohistochemistry
Transplants

Keywords

  • enteric nervous system
  • enteric neuropathies
  • fetal human intestine
  • xenotransplant

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

Cite this

Xenotransplantation of human intestine into mouse abdomen or subcutaneous tissue : Novel platforms for the study of the human enteric nervous system. / Nagy, N.; Marsiano, N.; Bruckner, R. S.; Scharl, M.; Gutnick, M. J.; Yagel, S.; Arciero, E.; Goldstein, A. M.; Shpigel, N. Y.

In: Neurogastroenterology and Motility, Vol. 30, No. 3, e13212, 01.03.2018.

Research output: Contribution to journalArticle

Nagy, N. ; Marsiano, N. ; Bruckner, R. S. ; Scharl, M. ; Gutnick, M. J. ; Yagel, S. ; Arciero, E. ; Goldstein, A. M. ; Shpigel, N. Y. / Xenotransplantation of human intestine into mouse abdomen or subcutaneous tissue : Novel platforms for the study of the human enteric nervous system. In: Neurogastroenterology and Motility. 2018 ; Vol. 30, No. 3.
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abstract = "Background: Current efforts to develop stem cell therapy as a novel treatment for neurointestinal diseases are limited by the unavailability of a model system to study cell transplantation in the human intestine. We propose that xenograft models support enteric nervous system (ENS) development in the fetal human intestine when transplanted into mice subcutaneously or intra-abdominally. Methods: Fetal human small and large intestine were grafted onto the small intestinal mesentery and into the subcutaneous tissue of immunodeficient mice for up to 4 months. Intestinal cytoarchitecture and ENS development were studied using immunohistochemistry. Key Results: In both abdominal and subcutaneous grafts, the intestine developed normally with formation of mature epithelial and mesenchymal layers. The ENS was patterned in two ganglionated plexuses containing enteric neurons and glia, including cholinergic and nitrergic neuronal subtypes. c-Kit-immunoreactive interstitial cells of Cajal were present in the gut wall. Conclusions & Inferences: Abdominal xenografts represent a novel model that supports the growth and development of fetal human intestine. This in vivo approach will be a useful method to study maturation of the ENS, the pathophysiology of neurointestinal diseases, and the long-term survival and functional differentiation of neuronal stem cells for the treatment of enteric neuropathies.",
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