Intramyocardial transplantation of bioartificial iPS-myocardial-splints for restauration of ischemic myocardium in a rat model. In vivo evaluation of survival and impact of transplated tissue on left ventricular function

最近的研究结果表明，由于有限的细胞存活和不利的生物分布，干细胞(衍生物)在心肌内的应用不能显著恢复受损的心肌。固体生物人工心肌组织移植(Bio-Artiated心脏组织，BCT)具有较好的疗效。然而，目前，具有足够大小和足够的血管供应的BCT的临床应用似乎还很遥远。作为另一种概念，我们倾向于应用多个小的BCT夹板(尺寸：6 mm x 1mm2)。新的心肌内植入技术应初步建立在基于新生心肌细胞的同种异体心肌夹板上，并在功能和组织学上与标准的心外膜植入的心肌夹板进行比较。之后，这些发现应该被转移到BCT-夹板上，这种夹板是由诱导的多能干细胞(MIPS)产生的。将MIPS-BCT夹板植入裸鼠慢性缺血心肌。MIPS-BCT是转基因的荧光素酶，因此这些MIPS-BCT的体内存活将使用荧光素酶生物成像进行28天的评估。功能分析将通过超声心动图、磁共振断层扫描和电导导管进行。本项目的目的是评估植入心肌内的BCT夹板是否能在复发性心肌中整合，从而改善左心泵功能。考虑到干细胞研究的最新进展，该方法将为基于iPS细胞的缺血心肌修复的临床应用带来新的前景。

Recent findings demonstrate that intramyocardial application of stem cell (derivates) do not significantly restore damaged myocardium due to limited cell survival and adverse biodistribution. The transplantation of solid bioartificial myocardial tissue (bioartificial cardiac tissue, BCT) results in better outcome. However, currently the clinical application of BCTs with adequate size and vascular supply seem to be far away. As an alternative conception we would favour the application of multiple of small BCT-splints (size: 6 mm x 1 mm2). These BCT-splints can potentionally neovascularize and couple functionally to the recipient´s myocardium.The new intramyocardial implantation technique should be primarily established using syngenic BCT-splints based on neonatal cardiomyocytes and compared functionally and histologically with standardized epicardially implantated BCT-splints. Afterwards, these findings should be transferred to BCT-splints which are generated from induced pluripotent stem cells of mice (miPS). The miPS-BCT-splints will be implanted in a chronic ischemic myocardium of nude rats. The miPS-BCTs are transgenic for luciferase, thus the in vivo survival of these miPS-BCTs will be evaluated for 28 days using Luciferase Bioimaging. Functional analyses will be performed by echocardiography, magnetic resonance tomography and conductance catheter. The goal of this project is to evaluate whether intramyocardially implanted BCT-splints functionally integrate in recpipients myocardium and consequently improve the left ventricular pump function. Considering recent progresses in stem cell research, this method would introduce new perspectives for the clinical application of iPS cell based restauration of ischemic myocardium.