Transserosal migration of enteric neural stem cells: Developing an avian colon model

J Pediatr Surg. 2018 Dec;53(12):2435-2439. doi: 10.1016/j.jpedsurg.2018.08.017. Epub 2018 Sep 2.

Abstract

Background: Stem cell transplantation is a potential therapy for enteric neuropathies, including Hirschsprung disease. Proof-of-principle has been obtained using focal transplants into neonatal mouse colon. The challenge now is to deliver stem cells to a large surface area to reconstruct an enteric nerve plexus. One proposed method is serosal application using a polymer membrane. However, transserosal migration of stem cells has not been demonstrated in mature colon. This study aimed to develop an avian model to demonstrate stem cell migration across the intact serosa of mature colon.

Methods: Hindguts were obtained from E14 quail embryos, transplanted onto E8 chicken chorioallantoic membranes and harvested after 2 and 8 days. Tissues were assessed immunohistologically for apoptosis (caspase-3), maturity (α-SMA), preservation of mucosa (E-cadherin), and preservation of serosa (cytokeratin).

Results: Transient necrosis of the central mucosa was observed over the first two days, followed by recovery. Twenty-three grafts were assessed immunohistologically at day 8. Nineteen grafts demonstrated progressive maturation and an intact mucosa. Circumferential serosal preservation was observed in 9 grafts. No apoptosis was seen.

Conclusion: Avian colon may be successfully harvested with an intact serosa. Large chorioallantoic membrane grafts remain viable for at least 8 days, and the serosa can be preserved throughout. This provides an economical platform for assessing transserosal migration of stem cells in mature colon.

Keywords: Enteric nervous system; Enteric neuropathy; Hirschsprung disease; Japanese quail; Stem cell therapy.

MeSH terms

  • Animals
  • Cadherins / metabolism
  • Caspase 3 / metabolism
  • Cell Movement / physiology*
  • Colon / metabolism*
  • Colon / transplantation
  • Enteric Nervous System / cytology*
  • Fluorescent Antibody Technique
  • Keratins / metabolism
  • Neural Stem Cells / metabolism*
  • Serous Membrane / cytology
  • Serous Membrane / metabolism*
  • Stem Cell Transplantation / methods

Substances

  • Cadherins
  • Keratins
  • Caspase 3