Sustained Release of Decoy Wnt Receptor (sLRP6E1E2)-Expressing Adenovirus Using Gel-Encapsulation for Scar Remodeling in Pig Model

利用凝胶封装技术持续释放诱饵 Wnt 受体 (sLRP6E1E2) 表达腺病毒,用于猪模型中的疤痕重塑

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作者:Chae-Eun Yang, Sewoon Choi, Ju Hee Lee, Eun Hye Kang, Hyo Min Ahn, Tai Suk Roh, Chae-Ok Yun, Won Jai Lee

Abstract

An adenoviral vector (Ad) expressing a Wnt decoy receptor (sLRP6E1E2) is known to induce an anti-fibrotic effect by inhibiting Wnt signaling. We evaluated its effects in vivo using pig models and attempted to introduce an alginate gel-matrix system to prolong the effect of the Ad. Transduction efficiency as to the biological activity of Ad in different forms was evaluated. Then, 50 days after the formation of full-thickness skin defects on the backs of Yorkshire pigs, scars were treated with each form of Ad. Therapeutic efficacy and various factors influencing scar formation and collagen rearrangement were analyzed. Inflammatory cell infiltration within the scar tissues was also evaluated. Decoy Wnt receptor (sLRP6E1E2)-expressing adenovirus treatment improved scar quality in a pig model. Loading this construct in alginate gel allows sustained virus release into local tissues and prolongs Ad activity, thus maintaining its therapeutic effect longer in vivo.

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