Bioreducible polymer-transfected skeletal myoblasts for VEGF delivery to acutely ischemic myocardium.
Bioreducible polymer-transfected skeletal myoblasts for VEGF delivery to acutely ischemic myocardium.
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DOI：
10.1016/j.biomaterials.2010.09.061
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发表时间：
2011-01
期刊：
影响因子：
14
通讯作者：
Kim, Sung Wan
中科院分区：
文献类型：
--
作者：
McGinn, Arlo N.;Nam, Hye Yeong;Ou, Mei;Hu, Norman;Straub, Catherine M.;Yockman, James W.;Bull, David A.;Kim, Sung Wan
将骨骼肌成肌细胞植入心脏已被研究作为心肌梗死后再生和保护心肌免受损伤的手段。虽然几项利用骨骼肌成肌细胞的动物研究报告了积极的发现，但临床研究的结果好坏参半。在这项研究中，我们利用一种新开发的生物可还原聚合物系统，在植入急性缺血心肌之前，用编码血管内皮生长因子（VEGF）的质粒转染骨骼肌成肌细胞。已证实VEGF促进心肌梗死后心肌的血管重建。我们报道了将表达VEGF的骨骼肌成肌细胞移植到急性缺血心肌中比移植未转染的骨骼肌成肌细胞产生了上级结果。表达分泌的VEGF的成肌细胞能够将心脏功能恢复到通过射血分数测量的非疾病水平，限制心脏腔室的重塑，并防止心肌壁变薄。此外，与未转染的成肌细胞相比，表达VEGF的骨骼肌成肌细胞显著改善了小动脉和毛细血管的形成、存活心肌细胞的保留和细胞凋亡的预防。这项工作证明了使用生物可还原阳离子聚合物来创建工程化骨骼肌成肌细胞以治疗急性缺血心肌的可行性。
Implantation of skeletal myoblasts to the heart has been investigated as a means to regenerate and protect the myocardium from damage after myocardial infarction. While several animal studies utilizing skeletal myoblasts have reported positive findings, results from clinical studies have been mixed. In this study we utilize a newly developed bioreducible polymer system to transfect skeletal myoblasts with a plasmid encoding vascular endothelial growth factor (VEGF) prior to implantation into acutely ischemic myocardium. VEGF has been demonstrated to promote revascularization of the myocardium following myocardial infarction. We report that implanting VEGF expressing skeletal myoblasts into acutely ischemic myocardium produces superior results compared to implantation of untransfected skeletal myoblasts. Skeletal myoblasts expressing secreted VEGF were able to restore cardiac function to non-diseased levels as measured by ejection fraction, to limit remodeling of the heart chamber as measured by end systolic and diastolic volumes, and to prevent myocardial wall thinning. Additionally, arteriole and capillary formation, retention of viable cardiomyocytes, and prevention of apoptosis was significantly improved by VEGF expressing skeletal myoblasts compared to untransfected myoblasts. This work demonstrates the feasibility of using bioreducible cationic polymers to create engineered skeletal myoblasts to treat acutely ischemic myocardium.
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影响因子：
37.8
作者：
Ye, Lei;Haider, Husnain Kh;Sim, Eugene K. W.
通讯作者：
Sim, Eugene K. W.
DOI：
10.1016/j.jtcvs.2009.02.018
发表时间：
2009-08-01
影响因子：
6
作者：
Hoashi, Takaya;Matsumiya, Goro;Sawa, Yoshiki
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影响因子：
10.8
作者：
Bull, DA;Bailey, SH;Kim, SW
通讯作者：
Kim, SW
影响因子：
5.1
作者：
Yockman, J. W.;Choi, D.;Bull, D. A.
通讯作者：
Bull, D. A.
影响因子：
37.8
作者：
Henry, TD;Annex, BH;McCluskey, ER
通讯作者：
McCluskey, ER