RHESUS HEART REGENERATION WITH EMBRYONIC STEM CELLS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。为了解决美国的主要死因心脏病，我们将测试一种新的基于细胞的治疗方式，以再生患病或受损的心肌。我们的目标是测试恒河猴胚胎干细胞(ES)在心肌梗死后再生心肌的能力。利用前些年建立的恒河猴心肌梗死模型，我们测试了梗塞相关动脉再灌注后经导管在冠状动脉内输送恒河猴胚胎干细胞的情况。我们的实验动物在输注2X107恒河猴ES细胞时表现出明显的无复流现象，导致靶向冠脉床的灌流消失。这一意想不到的结果导致了大面积心肌梗死的形成。我们能够在活体动物中使用心脏核磁共振成像追踪Ferridex(小顺磁氧化铁)标记的细胞。2个月后，根据MRI成像和病理评估，心肌内仍有大量细胞。基于这些结果，我们修改了我们的细胞输送方法，并尝试使用直接壁内注射而不是冠状动脉内注射的方法在心肌内输送细胞。本研究使用了WNPRC动物服务、WNPRC干细胞资源和WNPRC病理服务。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To address the major cause of death in the United States, heart disease, we will testing a new form of cell-based therapy to regenerate diseased or damaged myocardium. We aim to test the ability of rhesus embryonic stems (ES) cells to regenerate heart muscle following myocardial infarction. Utilizing the rhesus myocardial infarction model established in previous years, we have tested catheter based intracoronary artery delivery of rhesus embryonic stem cells post-reperfusion of the infarct related artery. Our pilot animal demonstrated significant no reflow phenomena with infusion of 2X107 rhesus ES cells resulting in obliteration of perfusion of the targeted coronary bed. This unanticipated result contributed to the formation of a large myocardial infarction. We were able to track Ferridex (small paramagnetic iron oxide) labeled cells using cardiac MRI imaging in living animals. A significant volume of cells remained in the myocardium based on MRI imaging and on pathology evaluation at 2 months. Based on these results we revised our cell delivery approach and piloted intramyocardial delivery of cells using direct intramural injection rather than intracoronary delivery. This research used WNPRC Animal Services; WNPRC Stem Cell resource; and WNPRC Pathology Services.