Nong Yibing, Guo Yiru, Tomlin Alex, Zhu Xiaoping, Wysoczynski Marcin, Li Qianhong, Bolli Roberto
Institute of Molecular Cardiology, University of Louisville, Louisville, KY, USA.
Diabetes and Obesity Center, University of Louisville, Louisville, KY, USA.
Mol Cell Biochem. 2021 May;476(5):2135-2148. doi: 10.1007/s11010-021-04077-6. Epub 2021 Feb 5.
In the field of cell therapy for heart disease, a new paradigm of repeated dosing of cells has recently emerged. However, the lack of a repeatable cell delivery method in preclinical studies in rodents is a major obstacle to investigating this paradigm. We have established and standardized a method of echocardiography-guided percutaneous left ventricular intracavitary injection (echo-guided LV injection) as a cell delivery approach in infarcted mice. Here, we describe the method in detail and address several important issues regarding it. First, by integrating anatomical and echocardiographic considerations, we have established strategies to determine a safe anatomical window for injection in infarcted mice. Second, we summarize our experience with this method (734 injections). The overall survival rate was 91.4%. Third, we examined the efficacy of this cell delivery approach. Compared with vehicle treatment, cardiac mesenchymal cells (CMCs) delivered via this method improved cardiac function assessed both echocardiographically and hemodynamically. Furthermore, repeated injections of CMCs via this method yielded greater cardiac function improvement than single-dose administration. Echo-guided LV injection is a feasible, reproducible, relatively less invasive and effective delivery method for cell therapy in murine models of heart disease. It is an important approach that could move the field of cell therapy forward, especially with regard to repeated cell administrations.
在心脏病细胞治疗领域,一种新的重复给药细胞范例最近出现了。然而,在啮齿动物的临床前研究中缺乏可重复的细胞递送方法是研究这一范例的主要障碍。我们已经建立并标准化了一种超声心动图引导的经皮左心室腔内注射方法(超声引导下左心室注射),作为梗死小鼠的细胞递送途径。在此,我们详细描述该方法并探讨与之相关的几个重要问题。首先,通过整合解剖学和超声心动图方面的考虑因素,我们制定了在梗死小鼠中确定安全注射解剖窗口的策略。其次,我们总结了使用该方法(734次注射)的经验。总体存活率为91.4%。第三,我们研究了这种细胞递送方法的疗效。与载体治疗相比,通过该方法递送的心脏间充质细胞(CMC)在超声心动图和血流动力学评估中均改善了心脏功能。此外,通过该方法重复注射CMC比单剂量给药产生了更大的心脏功能改善。超声引导下左心室注射是一种可行、可重复、侵入性相对较小且有效的心脏病小鼠模型细胞治疗递送方法。它是一种能够推动细胞治疗领域向前发展的重要方法,特别是在重复细胞给药方面。