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Retroviral Delivery of A Dominant Negative TGF‐beta Receptor II Mitigates Scar in a Rabbit Model of Scar Hypertrophy
Author(s) -
Reid Russell R.,
Roy Nakshatra,
Mogford Jon E.,
Zimmerman Hannah,
Lee Chung,
Mustoe Thomas A.
Publication year - 2004
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1067-1927.2004.0abstractau.x
Subject(s) - hypertrophic scar , transfection , receptor , medicine , green fluorescent protein , wound healing , transforming growth factor beta , mutant , pathology , andrology , microbiology and biotechnology , chemistry , immunology , biology , gene , biochemistry
Effective blockade of the pluripotent cytokine TGF‐beta 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 beta receptors within the wound milieu. Our goal was to examine the effects of dominant negative mutant TGF‐beta receptor II (dnTGFRII) 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 14 (two‐day injection group) or day 8, 10, 12 (three‐day injection group) post wounding. Delivery of a null vector (pMSCV‐GFP) at the same time points served as a negative control. Histomorphometric analysis of wounds harvested at day 28 revealed a statistically significant reduction (33%) in the scar elevation index in 2‐day treated and a more modest reduction in SEI (17.5%) in the 3‐day treated arm compared to null‐treated controls. Confocal microscopy confirmed stable transfection of the construct in both peri‐wound tissue as well as rabbit dermal fibroblasts transfected in vitro. Optimization of this novel application in retroviral gene therapy could lead to effective anti‐scarring strategies.