Human skin-derived precursor cells xenografted in aganglionic bowel.

J Pediatr Surg

Division of Pediatric Surgery, Department of Surgery, School of Medicine, Stanford University, Division of Pediatric Surgery, 300 Pasteur Drive, Alway M116, Stanford, CA 94305. Electronic address:

Published: December 2020

AI Article Synopsis

  • Hirschsprung disease affects 1 in 5000 newborns annually in the U.S., and researchers are exploring using neural crest stem cells to restore the enteric nervous system.
  • Human skin-derived precursor cells (hSKPs) were cultured and injected into juvenile minipigs with chemically induced aganglionosis to study their behavior post-transplantation.
  • After a week, hSKPs were found in the pig's colons, showing signs of neuroglial differentiation, indicating their potential for treating Hirschsprung disease.

Article Abstract

Purpose: One in 5000 newborns is diagnosed with Hirschsprung disease each year in the United States. The potential of employing neural crest stem cells to restore the enteric nervous system has been investigated. Skin-derived precursor cells (SKPs) are multipotent progenitor cells that can differentiate into neurons and gliocytes in vitro and generate enteric ganglion-like structures in rodents. Here we examined the behavior of human SKPs (hSKPs) after their transplantation into a large animal model of colonic aganglionosis.

Methods: Juvenile minipigs underwent a chemical denervation of the colon to establish an aganglionosis model. The hSKPs were generated from human foreskin and were cultured in neuroglial-selective medium. Cells were labeled with a fluorescent dye and were injected into the porcine aganglionic colon. After one week, transplanted hSKPs were assessed by immunofluorescence for markers of multipotency and neuroglial differentiation.

Results: In culture, hSKPs expressed nestin and S100b indicative of neuroglial precursors. After xenografting in pigs, hSKPs were identified in the myenteric and submucosal plexuses of the colons. The hSKPs expressed nestin and early neuroglial differentiation markers.

Conclusions: Human SKPs transplanted into aganglionic colon demonstrated immunophenotypes of neuroglial progenitors, suggesting their potential use for Hirschsprung disease.

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http://dx.doi.org/10.1016/j.jpedsurg.2020.03.006DOI Listing

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