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rAd‐p21 Significantly Attenuates Granulation Tissue Formation and Scar Thickness In Vivo
Author(s) -
Gu DL.,
Atencio I.,
Looper D.,
Kang D.W.,
Maneval D.,
Zepeda M.
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.1067-1927.2004.0abstractat.x
Subject(s) - in vivo , granulation tissue , platelet derived growth factor receptor , chemistry , cell growth , in vitro , microbiology and biotechnology , andrology , wound healing , growth factor , biology , medicine , immunology , biochemistry , receptor
Excessive scarring is a significant clinical problem. p21, a cyclin‐dependent kinase inhibitor, blocks cell cycle progression and attenuates proliferation of various cell types. Our in vitro rAd‐p21 dose response studies of primary human dermal fibroblasts showed a 3–80 fold reduction of cell proliferation as measured by BrdU incorporation at doses of 1 × 10 8 −3 × 10 9 PN/mL, respectively. Further, rAd‐p21 at 3 × 10 9 PN/mL showed a 2‐fold less procollagen I (PIP) production when compared to control virus. These in vitro data demonstrate that rAd‐p21 significantly attenuates fibroproliferation and procollagen production in the target cells. In vivo , a rat PVA sponge model was used. rAd‐p21, at doses of 1 × 10 9 , 1 × 10 10 and 5 × 10 10 PN was delivered into sponges that had previously been treated with a granulation tissue stimulator, rAd‐PDGF‐B. Results showed that sponges receiving rAd‐PDGF‐B alone had the highest % granulation fill (40–60% fill area). Sponges that were treated with rAd‐PDGF‐B for the first injection followed by rAd‐p21 on a second injection showed a dose‐dependent decrease in % granulation fill as rAd‐p21 doses increased ( p < 0.001). On day 5 post‐injection, IHC staining identified p21 protein expression only in sponges receiving rAd‐p21. In addition, the quantitative measurement of cells labeled by BrdU or Ki67 demonstrated that rAd‐p21 significantly attenuated cell proliferation when compared to rAd‐PDGF alone in this model ( p < 0.01). In another in vivo experiment, a rabbit excessive scar model was used. rAd‐p21, at a dose of 2 × 10 9 PN/wound was intradermally injected into the rabbit ear wounds that had previously been treated with PDGF‐BB protein. Preliminary data showed that scar thickness in rAd‐p21 treated wounds was significantly decreased in comparison to wounds treated with the control virus ( p < 0.05). These data suggest that rAd‐p21 is effective in attenuating scars in the rabbit ear excessive scar model. Our in vitro and in vivo data support the further exploration of rAd‐p21 as a useful therapeutic candidate for hyperproliferative diseases in patients.