Permissive environment in postnatal wounds induced by adenoviral-mediated overexpression of the anti-inflammatory cytokine interleukin-10 prevents scar formation

doi:10.1111/j.1524-475X.2007.00326.x

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Wiley InterScience

Wound Repair and Regeneration

Volume 16 Issue 1, Pages 70 - 79

Published Online: 13 Dec 2007

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Permissive environment in postnatal wounds induced by adenoviral-mediated overexpression of the anti-inflammatory cytokine interleukin-10 prevents scar formation

Ashley Gordon, MD ^1,2 ^§ ; Elliott D. Kozin, MD ^1,2 ^§ ; Sundeep G. Keswani, MD ^1,2 ^§ ; Sachin S. Vaikunth, MD ¹ ; Anna B. Katz, MD ^1,2 ; Philip W. Zoltick, MD ² ; Michele Favata, PhD ³ ; Antoneta P. Radu, MS ² ; Louis J. Soslowsky, PhD ³ ; Meenhard Herlyn, DVM ⁴ ; Timothy M. Crombleholme, MD ^1,2,4

1. Center for Molecular Fetal Therapy, Division of General, Thoracic and Fetal Surgery, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College Of Medicine, Cincinnati, Ohio,
2. Division of General, Thoracic, and Fetal Surgery, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,
3. The Department of Orthopedic Research, The University of Pennsylvania School of Medicine, and
4. The Wistar Institute, Philadelphia, Pennsylvania

Correspondence to Reprint requests:
Timothy M. Crombleholme, The Center for Molecular Fetal Therapy, Division of General, Thoracic, and Fetal Surgery, Cincinnati Children's Hospital Medical Center, 3333 Burnett Avenue, Cincinnati, OH.
Tel: 513 636 9608;
Fax: 513 636 7657;
Email: timothy.crombleholme@cchmc.org

Supported in part by a grant from the NIDDK (TMC) R01-DK59242.

^§These authors contributed equally to this work.

ABSTRACT

Wound healing in the mid-gestation fetus is scarless with minimal inflammation and a unique extracellular matrix. We have previously documented the relative lack of inflammatory cytokines in this environment. We demonstrate that interleukin (IL)-10 is highly expressed in mid-gestation human fetal skin but is absent in postnatal human skin. We hypothesize that overexpression of IL-10 in postnatal skin may replicate a permissive environment for scarless healing. To study the mechanism underlying this process we performed immunohistochemistry for IL-10 in human mid-gestation fetal and postnatal skin. We also determined if adenoviral-mediated overexpression of IL-10 could allow for scarless wound healing in a murine incisional wound model. Wounds were analyzed at 1–90 days postwounding for effects on scar formation, inflammatory response, and biomechanical properties. Ad-IL-10 reconstitutes a permissive environment for scarless healing as shown by reconstitution of a normal dermal reticular collagen pattern and distribution of dermal elements. Compared with controls, Ad-IL-10 treated wounds showed reduced inflammatory response and no difference in biomechanical parameters. Therefore, overexpression of IL-10 in postnatal wounds results in a permissive environment for scarless wound repair, possibly by replicating a fetal wound environment.

Manuscript received: 24 October 2006
Accepted in final form: 25 July 2007

DIGITAL OBJECT IDENTIFIER (DOI)

10.1111/j.1524-475X.2007.00326.x About DOI