Myocardial Cellular Stimulation of Angiogenesis

血管生成的心肌细胞刺激

• 批准号: 7735008
• 负责人: Keith A Horvath
• 金额: $ 36.6万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7735008
• 关键词: Aftercare; Animal Model; Autologous; Blood Vessels; Bone Marrow; Carbon Dioxide; Chronic; Cine Magnetic Resonance Imaging; Clinical; Devices; End Point; Family suidae; Growth; Heart; Histologic; Histology; Holmium; Injury; Ischemia; Lasers; Life; Light; Magnetic Resonance Imaging; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Methods; Modeling; Myocardial; Myocardial Ischemia; Patients; Rest; Stress Echocardiography; Tissues; Week; angiogenesis; improved; interest; paracrine; response; success; Aftercare; Animal Model; Autologous; Blood Vessels; Bone Marrow; Carbon Dioxide; Chronic; Cine Magnetic Resonance Imaging; Clinical; Devices; End Point; Family suidae; Growth; Heart; Histologic; Histology; Holmium; Injury; Ischemia; Lasers; Life; Light; Magnetic Resonance Imaging; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Methods; Modeling; Myocardial; Myocardial Ischemia; Patients; Rest; Stress Echocardiography; Tissues; Week; angiogenesis; improved; interest; paracrine; response; success

The stimulation of myocardial angiogenesis may be an important method to diminsh ischemia and improve the quality of patients' lives. Transmyocardial laser revascularization (TMR)is one such method that employs the use of a high powered laser to create a controlled injury and engender the natural angiogenic response. While clinical results with two different wavelengths of laser light are reportedly similar there are vast differences between the laser tissue interactions. We investigated whether this difference led to a myocardial functional change and whether the mechanisms whereby each laser achieves its clinical success is different. Employing a porcine model of chronic myocardial ischemia; cine MRI, hyperenhancement MRI, rest and stress echocardiography and histology were performed after TMR. There were significant improvements in myocardial function after treatment by a carbon dioxide that were not seen when a holmium:YAG device was used. Histology and MRI confirmed more scarrring and less angiogenesis with the Ho:YAG device at 6 weeks post treatment. Building on these results we have embarked on the addition of cellular therapy to further enhance the angiogenic response engendered by the laser. Using autologous bone marrow which has been allowed to differentiate and expand, mesenchymal stem cells are injected into the ischemic zone of the aforementioned large animal model. MRI, echo and histologic endpoints are being gathered to determine if a synergistic response is possible.

心肌血管生成的刺激可能是减少缺血并改善患者生活质量的重要方法。经胸膜激光血运重建（TMR）就是一种采用高功率激光来产生受控损伤并产生自然血管生成反应的方法。 尽管据报道，具有两种不同波长的激光光的临床结果相似，但激光组织相互作用之间存在巨大差异。 我们调查了这种差异是否导致心肌功能变化，以及每个激光获得其临床成功的机制是否不同。 采用慢性心肌缺血的猪模型； TMR后进行了Cine MRI，超增强MRI，休息和应力超声心动图和组织学。 二氧化碳治疗后，心肌功能得到了显着改善，而二氧化碳：使用了holmium：使用YAG装置。 在治疗后6周，组织学和MRI证实使用HO：YAG装置的疤痕和血管生成更少。 在这些结果的基础上，我们开始添加细胞疗法，以进一步增强激光产生的血管生成反应。 使用已允许分化和扩展的自体骨髓，将间充质干细胞注入上述大型动物模型的缺血区。 正在收集MRI，ECHO和组织学终点，以确定是否可以进行协同反应。