Cortical Bone Stem Cell Therapy for the Infarcted Heart

项目总结： 缺血性心脏病可导致心肌梗死(MI)，这是发病率和 全球范围内的死亡率。在受影响区域形成心肌梗死疤痕后，心脏扩张，心功能 抑郁，会导致心力衰竭。目前的治疗方法并不能逆转或减少心绞痛的死亡 心肌梗死引起的组织。细胞疗法可能是治疗心肌梗死后重塑的新策略，但到目前为止 在很大程度上无效。我们最近发现了一种新的干细胞，它位于 骨基质，我们称之为皮质骨干细胞(CBSCs)。我们已经证明，在小鼠MI中 模型，心肌梗死后CBSCs缩小瘢痕面积，增强心功能。这些有益的影响 似乎是由旁分泌机制介导的，我们已经证明了旁分泌机制可以保护心脏， 血管生成和免疫调节。拟议的研究是下一步确定这些 细胞可能对治疗心肌梗死患者有用。这项研究的目的是 确定最佳CBSC剂量、途径和时间以诱导更有效的心脏修复 猪MI模型。我们还将确定CBSCs是否通过心脏保护改善MI后重塑， 血管生成、心脏生成和/或免疫调节作用。我们提议的研究应该会提供新的 关于如何使用细胞疗法改善心肌梗死后心脏结构和功能的见解。

Project Summary: Ischemic heart disease can lead to myocardial infarction (MI), a major cause of morbidity and mortality worldwide. After MI scar forms in the affected region, the heart dilates, and cardiac function is depressed and can lead to heart failure. Current therapies do not reverse or reduce the death of tissue caused by MI. Cell therapy could be a new strategy to treat post MI remodeling, but to date has been largely ineffective. We have recently identified a novel stem cell that resides deep within the bone stroma, which we term Cortical Bone Stem Cells (CBSCs). We have shown, in a mouse MI model, that CBSCs reduce scar size and enhance cardiac function after MI. These beneficial effects appear to be mediated by paracrine mechanisms that we have shown can be cardioprotective, angiogenic, and immune modulatory. The proposed research is the next step in determining if these cells might be useful to treat patients who have suffered an MI. The Aims of this research are to determine the best CBSC dose, route and time of delivery to induce more effective cardiac repair in a swine MI model. We will also determine if CBSCs improve post MI remodeling by cardioprotective, angiogenic, cardiogenic and/or immune modulatory effects. Our proposed study should provide novel insights into how to use cell therapy to improve cardiac structure and function after MI.