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Human skin-derived precursor cells xenografted in aganglionic bowel
Anne-Laure Thomas1, Jordan S Taylor1, James C Y Dunn1
1Division of Pediatric Surgery, Department of Surgery, School of Medicine, Stanford University, Division of Pediatric Surgery, 300 Pasteur Drive, Alway M116, Stanford, CA 94305.
Journal of Pediatric Surgery
|April 8, 2020
Summary
Human skin-derived precursor cells (hSKPs) show potential for treating Hirschsprung disease. When transplanted into a pig model, hSKPs differentiated into neural cells, suggesting a future therapeutic avenue.
Area of Science:
- Stem cell biology
- Developmental biology
- Gastroenterology
Background:
- Hirschsprung disease affects 1 in 5000 newborns, involving the absence of nerve cells in the colon.
- Neural crest stem cells offer potential for restoring the enteric nervous system.
- Skin-derived precursor cells (SKPs) can differentiate into neural cells and form enteric ganglia.
Purpose of the Study:
- To investigate the behavior of human SKPs (hSKPs) after transplantation into a large animal model of Hirschsprung disease (colonic aganglionosis).
Main Methods:
- A large animal model of colonic aganglionosis was created in juvenile minipigs via chemical denervation.
- Human SKPs were cultured in a neuroglial-selective medium.
- Labeled hSKPs were injected into the aganglionic colon and assessed for multipotency and neuroglial differentiation markers via immunofluorescence after one week.
Main Results:
- In vitro, hSKPs expressed nestin and S100b, indicating neuroglial precursor status.
- Following xenotransplantation into the porcine colon, hSKPs were detected within the myenteric and submucosal plexuses.
- Transplanted hSKPs exhibited markers of early neuroglial differentiation.
Conclusions:
- Human SKPs transplanted into an aganglionic colon exhibited phenotypes consistent with neuroglial progenitors.
- These findings suggest the potential therapeutic utility of hSKPs for Hirschsprung disease.
