572. rAd-p21 To Reduce Excessive Dermal Scarring: Efficacy, Expression, and Tensile Strength in Animal Models

• Published in: Molecular therapy Vol. 13; no. S1; p. S220
• Main Authors: Kang, David W., Gu, Dan-Ling, Looper, L. David, Sugarman, Barry J., Quijano, Erlinda M., Zepeda, Monica L.
• Format: Journal Article
• Language: English
• Published: Milwaukee Elsevier Limited 01.05.2006
• Subjects: Adenoviruses; Bone marrow; Cyclin-dependent kinases; Kinases; Mineralization; Phosphatase; Proteins; Scars; Stem cells; Tensile strength
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1016/j.ymthe.2006.08.645

Excessive scarring is a significant clinical problem, resulting in both adverse tissue form and function. We have previously demonstrated that a recombinant adenovirus encoding the cyclin-dependent kinase inhibitor p21 (rAd-p21), attenuated cell proliferation at the wound site (Gu, et al., Wound Rep Reg 2005). In the studies described here, we demonstrate rAd-p21 DNA presence and p21 RNA expression at the wound site for at least 2 weeks in a rabbit ear model of scar formation. Further, we show that 2x10 6 particles of rAd-p21 reduced scar elevation by 20% in a rabbit ear scar model when compared to treatment with either a vehicle or a control adenovirus not containing a transgene (rAd-Empty). To investigate the potential effect of rAd-p21 on wound strength, we tested wounded tissue treated with rAd-p21 in vivo using tensile strength as an endpoint. Included in the experimental rat model were comparisons with other clinically relevant antiproliferative agents. Specifically, rAd-p21 at doses from 1x10 7 to 3.8x1010 particles per incision was administered intradermally to linear incisions, and wound strength was assayed 14-28 days post treatment. High doses of rAd-p21 (≥3x1010 particles) resulted in a mild and transient reduction of tensile strength, whereas low to moderate doses (1x107 to 1x1010 particles) had no significant effect on wound strength. Importantly, all rAd-p21 treated wounds regained tensile strength indistinguishable from vehicle treatment within 4 weeks of treatment. High dose rAd-Empty showed a subtle reduction in tensile strength that was only statistically significant at day 21. 100uL of triamcinolone at 5mg/mL/wound, 5-FU at 10mg/mL/wound, and low doses of MMC did not significantly reduce tensile strength, although high doses of MMC (0.2mg/mL/wound) severely reduced tensile strength, and wounds failed to heal completely by 28 days. Morphological analysis of all treatment groups revealed necrosis only in animals treated with MMC. These data suggest that rAd- p21 can minimize excessive scar formation in animals with minimal effects on wound strength.