Reduction of hypertrophic scar via retroviral delivery of a dominant negative TGF-β receptor II

Reid, Russell R.; Roy, Nakshatra; Mogford, Jon E.; Zimmerman, Hannah; Lee, Chung; Mustoe, Thomas A.

doi:10.1016/j.bjps.2005.12.026

« Previous Next »Journal of Plastic, Reconstructive & Aesthetic Surgery
Volume 60, Issue 1 , Pages 64-72, January 2007

Reduction of hypertrophic scar via retroviral delivery of a dominant negative TGF-β receptor II☆

Russell R. Reid
- Division of Plastic Surgery, Feinberg School of Medicine, Northwestern University, 675 North Saint Clair, Suite 19-250, Chicago, IL 60611, USA
Nakshatra Roy
- Department of Surgery, Wound Healing Research Lab, Northwestern University, 300 East Superior Street, Room 4-720, Chicago, IL 60611, USA
Jon E. Mogford
- Department of Surgery, Wound Healing Research Lab, Northwestern University, 300 East Superior Street, Room 4-720, Chicago, IL 60611, USA
Hannah Zimmerman
- Department of Surgery, Wound Healing Research Lab, Northwestern University, 300 East Superior Street, Room 4-720, Chicago, IL 60611, USA
Chung Lee
- Department of Urology, Northwestern University, 300 East Superior Street, 11-715 CHT 229, Chicago, IL 60611, USA
Thomas A. Mustoe
- Division of Plastic Surgery, Feinberg School of Medicine, Northwestern University, 675 North Saint Clair, Suite 19-250, Chicago, IL 60611, USA
- Corresponding author. Division of Plastic Surgery, Department of Surgery, Feinberg School of Medicine, Northwestern University, 675 North Saint Clair, Suite 19-250, Chicago, IL 60611, USA. Tel.: +1 312 695 6022; fax: +1 312 695 5672.

Received 5 February 2005; accepted 7 December 2005. published online 10 April 2006.

Summary

Effective blockade of the pluripotent cytokine transforming growth factor (TGF)-β as a means of cutaneous scar reduction is a strategy with great potential. This desired effect may be achieved through the overexpression of mutant TGF-β receptors within the wound milieu. Our goal was to examine the effects of dominant negative mutant TGF-β receptor II (TGFβRIIdn) protein expression in a well-established rabbit ear model of hypertrophic scarring. Serial injections of a retroviral construct encoding a truncated TGFβRII and the marker green fusion protein (pMSCV-rIIdn-GFP) were performed in 7mm punch wounds at day 10 and day 12 (two-day injection group) or days 8, 10, 12 (three-day injection group) post-wounding. Delivery of an empty vector (pMSCV-GFP) at the same time points served as a negative control. Histomorphometric analysis of wounds harvested at day 28 revealed a modest, though statistically significant reduction (20%, p=0.027) in the scar elevation index (SEI) in two-day treated and a more modest reduction in SEI (12%) in the three-day treated arm compared to null-treated controls. Confocal microscopy confirmed stable, yet variable transfection of the construct in both peri-wound tissue as well as rabbit dermal fibroblasts transfected in vitro. Optimisation of this novel application in retroviral gene therapy could lead to effective anti-scarring strategies.