Castro Liesa, Geertz Birgit, Reinsch Marina, Aksehirlioglu Bülent, Hansen Arne, Eschenhagen Thomas, Reichenspurner Hermann, Weinberger Florian, Pecha Simon
Department of Cardiovascular Surgery, University Heart Center Hamburg; partner site Hamburg/Kiel/Lübeck, German Centre for Cardiovascular Research (DZHK).
Department of Experimental Pharmacology and Toxicology, Cardiovascular ResearchCenter, University Medical Center Hamburg-Eppendorf.
J Vis Exp. 2019 Mar 18(145). doi: 10.3791/58810.
Due to the limited regeneration capacity of the heart in adult mammals, myocardial infarction results in an irreversible loss of cardiomyocytes. This loss of relevant amounts of heart muscle mass can lead to the heart failure. Besides heart transplantation, there is no curative treatment option for the end-stage heart failure. In times of organ donor shortage, organ independent treatment modalities are needed. Left-ventricular assist devices are a promising therapy option, however, especially as destination therapy, limited by its side-effects like stroke, infections and bleedings. In recent years, several cardiac repair strategies including stem cell injection, cardiac progenitors or myocardial tissue engineering have been investigated. Recent improvements in cell biology allow for the differentiation of large amounts of cardiomyocytes derived from human induced pluripotent stem cells (iPSC). One of the cardiac repair strategies currently under evaluation is to transplant artificial heart tissue. Engineered heart tissue (EHT) is a three-dimensional in vitro created cardiomyocyte network, with functional properties of native heart tissue. We have created EHT-patches from hiPSC derived cardiomyocytes. Here we present a protocol for the induction of left ventricular myocardial cryoinjury in a guinea pig, followed by implantation of hiPSC derived EHT on the left ventricular wall.
由于成年哺乳动物心脏的再生能力有限，心肌梗死会导致心肌细胞不可逆转的损失。相关数量的心肌质量损失会导致心力衰竭。除了心脏移植外，终末期心力衰竭没有治愈性的治疗选择。在器官供体短缺的时代，需要不依赖器官的治疗方式。左心室辅助装置是一种有前景的治疗选择，然而，尤其是作为终末期治疗时，会受到中风、感染和出血等副作用的限制。近年来，已经研究了几种心脏修复策略，包括干细胞注射、心脏祖细胞或心肌组织工程。细胞生物学的最新进展使得能够从人诱导多能干细胞（iPSC）分化出大量心肌细胞。目前正在评估的一种心脏修复策略是移植人工心脏组织。工程心脏组织（EHT）是一种在体外创建的三维心肌细胞网络，具有天然心脏组织的功能特性。我们已经用源自hiPSC的心肌细胞创建了EHT贴片。在此，我们展示了一种在豚鼠中诱导左心室心肌冷冻损伤的方案，随后将源自hiPSC的EHT植入左心室壁。
