Development of a biological ventricular assist device (BioVAD)
Development of a biological ventricular assist device (BioVAD)
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生物心室辅助装置（BioVAD）的开发
DOI：
10.1055/s-0029-1191571
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发表时间：
2009
影响因子：
1.5
通讯作者：
W. Zimmermann
中科院分区：
文献类型：
--
作者：
Y. Yildirim;H. Naito;M. Didié;B. Karikkineth;D. Biermann;T. Eschenhagen;H. Reichenspurner;W. Zimmermann
目的：工程心脏组织（EHT）已被用于修复体内局部心肌缺陷。在这项研究中，我们假设可以生成袋状心肌结构，可用作体内生物心室辅助装置 (BioVAD)。 方法：用新生大鼠心脏细胞、I 型胶原蛋白和含血清培养基在定制铸模中构建袋状 EHT。在这些条件下，7 天内形成球形结构（内/外径：10/12 毫米）。在柔性支架上继续额外培养 7 天以支持肌张力不全收缩。通过共焦激光扫描显微镜进行形态分析。在等长条件下评估收缩功能。 EHT 移植物被植入（n=15）健康的免疫抑制 Wistar 大鼠中。植入后 14 天对移植物形态和血管化进行组织学研究。结果：袋状 EHT 包含由连接蛋白 43 互连的心肌细胞组成的致密网络和由脯氨酰羟化酶阳性细胞组成的心内膜/心外膜表面衬里。袋状 EHT 可自发跳动，并显示出天然心肌的收缩特性，包括对钙和异丙肾上腺素的正性肌力反应。植入后十四天，EHT 移植物（n = 12）稳定地覆盖各自心脏的心外膜表面。移植的 EHT 由基质和分化的心肌以及部分来自供体的新形成的血管组成。结论：可以生成袋状 EHT，其具有对正性肌力药物也有反应的天然心肌的结构和功能特性。植入研究证明了它们作为心肌移植物的适用性，为评估 EHT 袋作为体内生物心室辅助装置奠定了基础。
Objective: Engineered heart tissue (EHT) has been used to repair local heart muscle defects in vivo. In this study, we hypothesized that pouch-like heart muscle constructs can be generated that may be utilized as biological ventricular assist devices (BioVADs) in vivo.Methods: Pouch-like EHTs were constructed from neonatal rat heart cells, collagen type I, and serum containing culture medium in custom made casting molds. Under these conditions spheroidal constructs formed within 7 days (inner/outer diameter: 10/12mm). Additional culturing was continued for 7 days on flexible holders to support auxotonic contractions. The morphological analysis was perfomed by confocal laser scanning microscopy. Contractile function was assessed under isometric conditions. EHT-grafts were implanted (n= 15) in healthy immune suppressed Wistar rats. Graft morphology and vascularization was studied histologically 14 days after implantation.Results: Pouch-like EHTs contain a dense network of connexin 43 interconnected cardiomyocytes and an endo-/epicardial surface lining composed of prolylhydroxylase positive cells. Pouch-like EHTs beat spontaneously and show contractile properties of native heart muscle including positive inotropic responses to calcium and isoprenaline. Fourteen days after implantation, EHT-grafts (n= 12) stably covered the epicardial surface of the respective hearts. Engrafted EHTs were composed of matrix and differentiated cardiac muscle as well as newly formed vessels which were partly donor-derived.Conclusions: Pouch-like EHTs can be generated with structural and functional properties of native myocardium responding also to inotropes. Implantation studies demonstrated their applicability as cardiac muscle grafts, setting the stage for an evaluation of EHT-pouches as biological ventricular assist devices in vivo.