کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4299909 1288404 2015 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Acellular dermal matrix-based gene therapy augments graft incorporation
ترجمه فارسی عنوان
ژن درمانی مبتنی بر ماتریکس پوستی است که باعث ایجاد پیوند می شود
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی عمل جراحی
چکیده انگلیسی

BackgroundAcellular dermal matrix (ADM) is widely used for structural or dermal replacement purposes. Given its innate biocompatibility and its potential to vascularize, we explored the possibility of ADM to function as a small interfering RNA (siRNA) delivery system. Specifically, we sought to improve ADM vascularization by siRNA-mediated inhibition of prolyl hydroxylase domain-2 (PHD2), a cytoplasmic protein that regulates hypoxia inducible factor-1α, and improve neovascularization.Materials and methodsFluorescently labeled siRNA was used to rehydrate thin implantable ADM. Pharmacokinetic release of siRNA was determined. Twelve millimeter sections of ADM reconstituted with PHD2 siRNA (nonsense siRNA as control) and applied to dorsal wounds of 40 FVB mice. Grafts were sewn in, bolstered, and covered with occlusive dressings. Photographs were taken at 0, 7, and 14 d. Wounds were harvested at 7 and 14 d and analyzed (messenger RNA, protein, histology, and immunohistochemistry).ResultsRelease kinetics was first-order with 80% release by 12 h. By day 14, PHD2-containing ADM appeared viable and adherent, whereas controls appeared nonviable and nonadherent. Real-time reverse transcription-polymerase chain reaction demonstrated near-complete knockdown of PHD2, whereas vascular endothelial growth factor and FGF-2 were increased 2.3- and 4.7-fold. On enzyme-linked immunosorbent assay, vascular endothelial growth factor was increased more than fourfold and stromal cell-derived factor doubled. Histology demonstrated improved graft incorporation in treated groups. Immunohistochemical demonstrated increased vascularity measured by CD31 staining and increased new cell proliferation by denser proliferating cell nuclear antigen staining in treated versus controls.ConclusionsWe concluded that ADM is an effective matrix for local delivery of siRNA. Strategies to improve the matrix and/or genetically alter the local tissue environment can be envisioned.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Surgical Research - Volume 195, Issue 1, 1 May 2015, Pages 360–367
نویسندگان
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