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 7 mm 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.
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Published online: April 10, 2006
Accepted: December 7, 2005
Received: February 5, 2005
☆Presented at the 14th Annual Wound Healing Society Meeting, Atlanta, GA, 2004.
© 2006 The British Association of Plastic Surgeons. Published by Elsevier Inc. All rights reserved.
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- Reduction of hypertrophic scar via retroviral delivery of a dominant negative TGF-beta receptor IIJournal of Plastic, Reconstructive & Aesthetic SurgeryVol. 60Issue 1
- PreviewHypertrophic scars (HSs) can cause significant aesthetic and functional symptoms and to-date no optimal treatment has been established. Many causes have been associated with HS development but regardless, it presents with appearance of myofibroblasts and an abnormal deposition of extracellular matrix (ECM) collagens. This accumulation makes ECM a logical target for pharmacological interventions, and researchers are endeavouring to modify ECM metabolism.