Lang Cajetan Immanuel, Wolfien Markus, Langenbach Anne, Müller Paula, Wolkenhauer Olaf, Yavari Arash, Ince Hüseyin, Steinhoff Gustav, Krause Bernd Joachim, David Robert, Glass Änne
Department of Cardiology, University Hospital Rostock, Rostock, Germany.
Reference and Translation Center for Cardiac Stem Cell Therapy, University of Rostock, Rostock, Germany.
Cell Physiol Biochem. 2017;42(1):254-268. doi: 10.1159/000477324. Epub 2017 May 25.
Stem cell-based regenerative therapies for the treatment of ischemic myocardium are currently a subject of intensive investigation. A variety of cell populations have been demonstrated to be safe and to exert some positive effects in human Phase I and II clinical trials, however conclusive evidence of efficacy is still lacking. While the relevance of animal models for appropriate pre-clinical safety and efficacy testing with regard to application in Phase III studies continues to increase, concerns have been expressed regarding the validity of the mouse model to predict clinical results. Against the background that hundreds of preclinical studies have assessed the efficacy of numerous kinds of cell preparations - including pluripotent stem cells - for cardiac repair, we undertook a systematic re-evaluation of data from the mouse model, which initially paved the way for the first clinical trials in this field.
A systematic literature screen was performed to identify publications reporting results of cardiac stem cell therapies for the treatment of myocardial ischemia in the mouse model. Only peer-reviewed and placebo-controlled studies using magnet resonance imaging (MRI) for left ventricular ejection fraction (LVEF) assessment were included. Experimental data from 21 studies involving 583 animals demonstrate a significant improvement in LVEF of 8.59%+/- 2.36; p=.012 (95% CI, 3.7-13.8) compared with control animals.
The mouse is a valid model to evaluate the efficacy of cell-based advanced therapies for the treatment of ischemic myocardial damage. Further studies are required to understand the mechanisms underlying stem cell based improvement of cardiac function after ischemia.
基于干细胞的再生疗法用于治疗缺血性心肌目前是深入研究的课题。在人类I期和II期临床试验中，已证明多种细胞群是安全的，并能发挥一些积极作用，然而仍缺乏疗效的确凿证据。虽然动物模型对于III期研究应用中适当的临床前安全性和疗效测试的相关性不断增加，但人们对小鼠模型预测临床结果的有效性表示担忧。在数百项临床前研究评估了包括多能干细胞在内的多种细胞制剂对心脏修复的疗效的背景下，我们对小鼠模型的数据进行了系统的重新评估，该模型最初为该领域的首次临床试验铺平了道路。
进行了系统的文献筛选，以确定报告小鼠模型中心脏干细胞疗法治疗心肌缺血结果的出版物。仅纳入使用磁共振成像（MRI）评估左心室射血分数（LVEF）的同行评审和安慰剂对照研究。来自21项研究、涉及583只动物的实验数据表明，与对照动物相比，LVEF显著提高了8.59%±2.36；p = 0.012（95%CI，3.7 - 13.8）。
小鼠是评估基于细胞的先进疗法治疗缺血性心肌损伤疗效的有效模型。需要进一步研究以了解缺血后基于干细胞改善心脏功能的潜在机制。
