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

生物人工 iPS 心肌夹板的心肌内移植用于恢复大鼠模型中的缺血心肌。

• 批准号: 230008316
• 负责人: Professor Dr. Ingo Kutschka
• 金额: --
• 依托单位: Klinik für Thorax-, Herz- und Gefäßchirurgie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/230008316?language=en
• 关键词: Intramyocardial; transplantation; bioartificial; iPS; myocardial

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.

最近的研究结果表明，心肌内应用干细胞（衍生物）不能显着恢复受损的心肌，由于有限的细胞存活和不利的生物分布。固体生物人工心肌组织（bioartificial cardiac tissue，BCT）移植效果较好。然而，目前具有足够尺寸和血管供应的BCT的临床应用似乎还很遥远。作为替代方案，我们倾向于应用多个小BCT夹板（尺寸：6 mm x 1 mm 2）。这些BCT-夹板可以潜在地新生血管并与受体心肌功能性耦合。新的心肌内植入技术应主要使用基于新生心肌细胞的同基因BCT-夹板，并与标准化心外膜移植的BCT-夹板进行功能和组织学比较。之后，这些发现应该转移到由小鼠诱导多能干细胞（miPS）产生的BCT夹板上。miPS-BCT-夹板将植入裸大鼠的慢性缺血心肌中。miPS-BCT是荧光素酶转基因的，因此将使用荧光素酶生物成像评价这些miPS-BCT的体内存活28天。将通过超声心动图、磁共振断层扫描和电导导管进行功能分析。本项目的目的是评估心肌内植入的BCT夹板是否在功能上与受体心肌整合，从而改善左心室泵功能。鉴于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开辟新的前景。

项目成果

Effect of natural killer cells on induced pluripotent stem cell-derived bioartificial cardiac tissue

自然杀伤细胞对诱导多能干细胞来源的生物人工心脏组织的影响

• DOI: 10.1055/s-0034-1367266
• 发表时间: 2014
• 期刊: Thoracic and Cardiovascular Surgeon
• 影响因子: 1.5
• 作者: Saito S;Kensah G;Baraki H;Dahlmann J;Haverich A;Hundrieser J;Martin U;Gruh I;Kutschka I
• 通讯作者: Kutschka I