Fetal wound healing using a genetically modified murine model: the contribution of P-selectin

J Pediatr Surg. 2008 Apr;43(4):675-82. doi: 10.1016/j.jpedsurg.2007.12.007.

Abstract

Purpose: During early gestation, fetal wounds heal with paucity of inflammation and absent scar formation. P-selectin is an adhesion molecule that is important for leukocyte recruitment to injury sites. We used a murine fetal wound healing model to study the specific contribution of P-selectin to scarless wound repair.

Methods: Linear excisional wounds were created on the dorsa of E15.5 and E17.5 gestation fetuses in wild-type and P-selectin (-/-) mice (term = 19 days). Wounds were harvested at various time-points after wounding and analyzed using histology and immunohistochemistry.

Results: The E15.5 wounds in both wild-type and P-selectin (-/-) fetuses healed scarlessly and with minimal inflammation, whereas E17.5 wounds healed with fibrosis and inflammation. However, the scars of the P-selectin (-/-) wounds appeared slightly different than wild-type. There were significantly more inflammatory cells in E17.5 wild-type wounds 6 hours after injury (P < .001), but the difference was no longer significant by 24 hours. Finally, reepithelialization was slower in the E15.5 knockout wounds compared to their wild-type counterparts.

Conclusions: Absence of P-selectin delays inflammatory cell recruitment and reepithelialization of fetal wounds; however, scar formation still occurs in late gestation wounds. The contribution of specific molecules to fetal wound healing can be elucidated using murine knockout or transgenic models.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Validation Study

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cicatrix / embryology
  • Cicatrix / metabolism
  • Fibrosis / embryology
  • Fibrosis / metabolism
  • Fibrosis / pathology
  • Immunohistochemistry
  • Inflammation / embryology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Keratinocytes / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Animal
  • P-Selectin / metabolism*
  • Wound Healing / physiology*
  • Wounds and Injuries / embryology*
  • Wounds and Injuries / metabolism*
  • Wounds and Injuries / pathology

Substances

  • P-Selectin