Recombinant adenovirus-p21 attenuates proliferative responses associated with excessive scarring

Excessive cutaneous scarring is an important clinical disorder resulting in adverse tissue growth and function as well as undesirable cosmetic appearance. p21WAF−1/Cip−1 is a cyclin‐dependent kinase inhibitor that blocks cell cycle progression and inhibits cell proliferation. We used a recombinant adenovirus containing the human p21WAF−1/Cip−1 cDNA (rAd‐p21) to evaluate proliferative responses in skin models. In vitro dose–response studies using primary human dermal fibroblasts resulted in a dose‐dependent expression of p21WAF−1/Cip−1 protein and a 3‐ to 80‐fold reduction in cell proliferation as measured by 5‐bromodeoxyuridine incorporation. Further, rAd‐p21 reduced type I procollagen production when compared to control virus. A rat polyvinyl alcohol sponge model was used to determine rAd‐p21 effects on granulation tissue formation in vivo. Sponges pretreated with a granulation tissue stimulator, rAd‐PDGF‐B and subsequently rAd‐p21 on a second injection, showed a p21WAF−1/Cip−1 specific dose‐dependent decrease in percent granulation fill as the rAd‐p21 dose increased (p