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Neurogastroenterol Motil. 2018 Mar;30(3). doi: 10.1111/nmo.13212. Epub 2017 Sep 8.

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

Author information

1
Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
2
Department of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
3
The Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel.
4
Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
5
Department of Obstetrics and Gynecology, Hadassah University Hospital, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.

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.

KEYWORDS:

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

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