Catheter-deliverable hydrogel derived from decellularized ventricular extracellular matrix increases endogenous cardiomyocytes and preserves cardiac function post-myocardial infarction.
Catheter-deliverable hydrogel derived from decellularized ventricular extracellular matrix increases endogenous cardiomyocytes and preserves cardiac function post-myocardial infarction.
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DOI：
10.1016/j.jacc.2011.10.888
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发表时间：
2012-02-21
影响因子：
24
通讯作者：
Christman, Karen L.
中科院分区：
文献类型：
--
作者：
Singelyn, Jennifer M.;Sundaramurthy, Priya;Johnson, Todd D.;Schup-Magoffin, Pamela J.;Hu, Diane P.;Faulk, Denver M.;Wang, Jean;Mayle, Kristine M.;Bartels, Kendra;Salvatore, Michael;Kinsey, Adam M.;DeMaria, Anthony N.;Dib, Nabil;Christman, Karen L.
本研究评价了来自心室细胞外基质（ECM）的可注射水凝胶用于治疗心肌梗死（MI）及其持续递送的能力。可注射材料为治疗MI提供了有前景的替代方案。虽然大多数检查的材料在小动物模型中显示出保留或改善的心脏功能，但没有一种是专门为心脏设计的，很少有转化为大型动物模型中的导管输送。我们已经开发了一种心肌特异性水凝胶，来自脱细胞心室ECM，在体内注射时自组装。雌性Sprague-Dawley大鼠进行缺血再灌注，2周后注射水凝胶或盐水。通过组织学和免疫组织化学评估植入反应，并在注射后1周使用程控电刺激检查胚胎发生的可能性。在注射前1周和MI后4周通过磁共振成像分析心脏功能。在猪模型中，我们使用NOGA引导的Myostar导管输送水凝胶，并利用组织学评估材料的保留。我们证明，在大鼠心肌梗死模型中注射该材料可增加梗死区的内源性心肌细胞，并维持心脏功能而不诱导心律失常。此外，我们证明了在猪模型中经血管内导管注射的可行性。据我们所知，这是第一个在大型动物模型中通过经内皮素注射递送的原位胶凝材料，这是将可注射材料转化为治疗人类心肌梗死的关键一步。我们的研究结果值得进一步研究这种材料在一个大的动物模型心肌梗死，并建议这可能是一个有前途的新疗法治疗心肌梗死。
This study evaluated the use of an injectable hydrogel derived from ventricular extracellular matrix (ECM) for treating myocardial infarction (MI) and its ability to be delivered percutaneously. Injectable materials offer promising alternatives to treat MI. While most of the examined materials have shown preserved or improved cardiac function in small animal models, none have been specifically designed for the heart and few have translated to catheter delivery in large animal models. We have developed a myocardial specific hydrogel, derived from decellularized ventricular ECM, which self-assembles when injected in vivo. Female Sprague-Dawley rats underwent ischemia reperfusion followed by injection of the hydrogel or saline 2 weeks later. The implantation response was assessed via histology and immunohistochemistry, and potential for arrhythmogenesis was examined using programmed electrical stimulation 1 week post-injection. Cardiac function was analyzed with magnetic resonance imaging 1 week pre-injection and 4 weeks post-MI. In a porcine model, we delivered the hydrogel using the NOGA guided Myostar catheter, and utilized histology to assess retention of the material. We demonstrate that injection of the material in the rat MI model increases endogenous cardiomyocytes in the infarct area and maintains cardiac function without inducing arrhythmias. Furthermore, we demonstrate feasibility of transendocardial catheter injection in a porcine model. To our knowledge, this is the first in situ gelling material to be delivered via transendocardial injection in a large animal model, a critical step towards the translation of injectable materials for treating myocardial infarction in humans. Our results warrant further study of this material in a large animal model of myocardial infarction and suggest this may be a promising new therapy for treating myocardial infarction.
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影响因子：
39.3
作者：
Freyman, T;Polin, G;Wilensky, RL
通讯作者：
Wilensky, RL
影响因子：
64.5
作者：
ARGRAVES, WS;DICKERSON, K;RUOSLAHTI, E
通讯作者：
RUOSLAHTI, E
影响因子：
14
作者：
Freytes, Donald O.;Martin, Jeffrey;Badylak, Stephen F.
通讯作者：
Badylak, Stephen F.
影响因子：
14.8
作者：
Huang, Ngan F.;Sievers, Richard E.;Lee, Randall J.
通讯作者：
Lee, Randall J.
影响因子：
3.3
作者：
Costandi, Peter N.;McCulloch, Andrew D.;Frank, Lawrence R.
通讯作者：
Frank, Lawrence R.