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ǥ : ȣ - 520014   186 
Thermo-sensitive And Biodegradable Polymeric Hydrogel-mediated Local Gene Transfer In Heart For Recovering Myocardial Infarction
전남대학교병원 심장센터, 전남대학교 심혈관질환 치료재생 특성화사업단, 과학기술부 제대혈 및 중간엽줄기세포 기능연구사업단
권진숙, 박인규, 김용숙, 홍문화, 조애신, 신선미, 김계훈, 박형욱, 홍영준, 김주한, 정명호, 조정관, 박종춘, 강정채, 안영근
Background: Successful application of local angiogenic gene therapy in heart will potentially reduce the mortality of patients suffering from ischemic heart disease. However, this success is greatly dependent upon delivery modality of therapeutic genes. Thermosensitive hydrogel-mediated local gene transfer is preferred in muscle, since release of DNA into surrounding tissue can be controlled by 3-dimensional network structure of hydrogel. Indeed, a system for controlled release of therapeutic gene may extend the duration of gene expression, especially in the clinical environment where longer gene expression is desirable after single injection. Here, thermo-sensitive and biodegradable polymeric hydrogel has been synthesized based on poloxamer and investigated for local gene transfer in heart in order to recover myocardial infarction. Methods: Initially, luciferase gene was delivered to heart in mouse to test the duration and intensity of gene expression. Bioluminescence optical imaging, luciferase assay, and histologic analyses were performed. Results: Gene expression intensity assessed by optical imaging is closely correlated to actual expressed protein measured by luciferase assay. Polymeric hydrogel-based gene transfer was shown to mediate enhanced gene expression up to 5 fold Total Flux (1day; 8983000 ± 4977000 p/sec/cm^2/sr) , compared to naked plasmid (1day; 1521000 ± 1477000 p/sec/cm^2/sr), p<0.05, and have two expression profiles with peaks at 2 days and around 25 days after local injection. Histologic analyses has revealed that high gene expression is initially dominated by myocardium, whereas lower and longer expression is mainly governed by fibrotic and/or inflammatory cells infiltrated into injury site during injection. Furthermore, fibrotic region is reduced with the injection of polymeric hydrogel, compared to that of plasmid only control, confirmed by Masson & Trichrome staining. Conclusions: Now we are investigating the efficacy of therapeutic genes delivered locally by this thermo-sensitive hydrogel in mouse or rat infarction model and results will be presented.


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