多模态成像检测干细胞联合功能化自组装多肽治疗急性心肌梗死

发布时间：2018-01-08 09:08

本文关键词：多模态成像检测干细胞联合功能化自组装多肽治疗急性心肌梗死　出处：《北京协和医学院》2017年博士论文　论文类型：学位论文

【摘要】：目的:利用摄取碘-131标记的ZGO的SD大鼠骨髓间充质干细胞(BMSCs),联合功能化自组装纳米多肽支架RADA-SKP注射至Balb/c小鼠急性梗死的心肌周围,利用超声心动、SPECT/CT、PET/CT多模态的影像手段,评估心功能变化,示踪BMSCs的定位、存活和迁移,评估心肌活性变化,同时结合病理结果,探讨功能化自组装多肽纳米支架材料提高干细胞在急性心肌梗死治疗中,提高治疗效果的可能性及其机制。方法:构建Balb/c小鼠的急性心肌梗死模型,分别在梗死心肌周围注射:A组(空白对照组):10%蔗糖溶液;B组(多肽对照组):功能化自组装纳米多肽支架RADA-SKP的蔗糖溶液;C组(细胞对照组):吞噬碘-131标记的ZGO的BMSCs;D组(多肽+细胞实验组):吞噬碘-131标记的ZGO的BMSCs联合功能化自组装纳米多肽支架RADA-SKP的蔗糖溶液。在术前1天和术后第1、7、14天行超声心动评估心功能;在术后第1、6、13天行SPECT/CT定位移植细胞;术后第2、14天行PET/CT评估梗死区域心肌活性。术后第14天取出心脏组织病理,行HE染色及CD34免疫组化。结果:心功能方面:利用功能化自组装多肽纳米支架RADA-SKP能够显著提高BMSCs对于小鼠心肌梗死模型的治疗效果。而单纯利用BMSCs治疗小鼠心肌梗死模型对于心功能的改善并无显著效果。干细胞定位方面:提示利用BMSCs联合功能化自组装纳米多肽支架进行治疗相较于单用BMSCs,能够使细胞更长时间的保持细胞的活性。梗死区域心肌活性方面:利用功能化自组装多肽RADA-SKP联合BMSCs对于小鼠心梗模型治疗相较于空白对照组和只移植功能化自组装多肽RADA-SKP组,能够显著改善心肌的活性。同时,在不联用功能化自组装多肽SKP的情况下,对于BMSCs修复梗死区域心肌的活性的修复,与联用功能化自组装多肽RADA-SKP的情况下,无显著性差异。结论:利用摄取碘-131标记的ZGO的大鼠BMSCs注射至Balb/c小鼠急性心肌梗死的心肌周围,利用超声心动、SPECT/CT、PET/CT多模态检测,可以有效的评估心功能变化,示踪BMSCs的定位、存活和迁移,评估心肌活性变化。单纯将SD大鼠BMSCs注射至Balb/c小鼠急性心肌梗死的心肌周围,可以改善心肌活性,但细胞存活时间较短,对于心功能的改善不明显;而联合功能化自组装纳米多肽支架RADA-SKP时,可以延长BMSCs在心肌中存活的时间,加强其诱导血管分化的作用,强化治疗效果。
[Abstract]:Objective: to investigate the effects of iodine 131 labeled ZGO on bone marrow mesenchymal stem cells (BMSCs) in SD rats. RADA-SKP was injected into the myocardium around acute infarction of Balb/c mice and SPECT / CT was used. PET/CT multimodal imaging method to assess cardiac function changes, trace the location, survival and migration of BMSCs, and evaluate myocardial activity changes, combined with pathological results. Objective: to explore the possibility and mechanism of functional self-assembled polypeptide nano-scaffold to improve the therapeutic effect of stem cells in acute myocardial infarction (AMI). Methods: the acute myocardial infarction model of Balb/c mice was established. Group A was injected with 10% sucrose solution around the infarct myocardium. Group B (polypeptide control group): sucrose solution of functionalized self-assembled nano-polypeptide scaffold RADA-SKP; Group C (cell control group): BMSCsphagocytosis of iodine-131 labeled ZGO; Group D (polypeptide cell test group). Phagocytosis of sucrose solution of iodo-131 labeled ZGO BMSCs combined with functionalized RADA-SKP nano-polypeptide scaffold. 1 day before and 1 day after operation. Cardiac function was evaluated by echocardiography on day 7 and 14; The transplanted cells were treated with SPECT/CT on the 1st day and 13th day after operation. Myocardial activity in the infarcted area was evaluated by PET/CT on the 2nd and 14th day after operation, and cardiac histopathology was taken out on the 14th day after operation. He staining and CD34 immunohistochemistry. Results: heart function:. The use of functionalized self-assembled polypeptide nano-scaffold RADA-SKP can significantly improve the therapeutic effect of BMSCs on myocardial infarction model in mice, while BMSCs alone can be used to treat myocardial infarction model in mice. There was no significant improvement in cardiac function. Stem cell localization:. It is suggested that BMSCs combined with functionalized self-assembled nano-polypeptide scaffold is more effective than BMSCs alone. The ability to keep cells alive for a longer period of time. Myocardial activity in infarcted areas:. Compared with control group and RADA-SKP group, functional self-assembled polypeptide (RADA-SKP) combined with BMSCs was used to treat myocardial infarction model in mice. At the same time, without the use of functional self-assembled polypeptide SKP, the repair of myocardial activity in infarcted area by BMSCs can be significantly improved. In conjunction with functionalized self-assembled polypeptide RADA-SKP. No significant difference was found. Conclusion: rat BMSCs with iodine-131-labeled ZGO was injected into the myocardium around the acute myocardial infarction of Balb/c mice and echocardiography was used. SPECT / CT / PET / CT multimodal detection can effectively evaluate cardiac function changes, trace the location, survival and migration of BMSCs. To evaluate the changes of myocardial activity. Injection of SD rat BMSCs into myocardium around acute myocardial infarction in Balb/c mice could improve myocardial activity, but the cell survival time was shorter. The improvement of cardiac function was not obvious. When RADA-SKP was combined with functionalized self-assembled nano-polypeptide scaffold, the survival time of BMSCs in myocardium was prolonged, the effect of inducing vascular differentiation was enhanced, and the therapeutic effect was enhanced.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R542.22

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