Wiernicki B, Rozwadowska N, Malcher A, Kolanowski T, Zimna A, Rugowska A, Kurpisz M
Department of Reproductive Biology and Stem Cells, Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
Department of Reproductive Biology and Stem Cells, Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
Int J Cardiol. 2016 Jan 1;202:710-21. doi: 10.1016/j.ijcard.2015.09.115. Epub 2015 Oct 22.
Myocardial infarction (MI) and left ventricle remodeling (LVR) are two of the most challenging disease entities in developed societies. Since conventional treatment cannot fully restore heart function new approaches were attempted to develop new strategies and technologies that could be used for myocardial regeneration. One of these strategies pursued was a cell therapy--particularly applying skeletal muscle stem cells (SkMCs).
Using NOD-SCID murine model of MI and human skeletal myoblast transplantation we were able to show that SkMC administration significantly affected gene expression profile (p<0.05) (NPPB, CTGF, GATA4, SERCA2a, PLB) of the heart ventricular tissue and this change was beneficial for the heart function. We have also shown, that the level of heart biomarker, NT-proBNP, decreased in animals receiving implanted cells and that the NT-proBNP level negatively correlated with left ventricle area fraction change (LVFAC) index which makes NT-proBNP an attractive tool in assessing the efficacy of cell therapy both in the animal model and prospectively in clinical trials.
The results obtained suggest that transplanted SkMCs exerted beneficial effect on heart regeneration and were able to inhibit LVR which was confirmed on the molecular level, giving hope for new ways of monitoring novel cellular therapies for MI.
心肌梗死(MI)和左心室重构(LVR)是发达社会中最具挑战性的两种疾病实体。由于传统治疗无法完全恢复心脏功能,人们尝试开发新的方法来制定可用于心肌再生的新策略和技术。其中一种采用的策略是细胞疗法——特别是应用骨骼肌干细胞(SkMCs)。
利用MI的NOD - SCID小鼠模型和人骨骼肌成肌细胞移植,我们能够证明给予SkMCs显著影响心室组织的基因表达谱(p<0.05)(NPPB、CTGF、GATA4、SERCA2a、PLB),并且这种变化对心脏功能有益。我们还表明,接受植入细胞的动物中心脏生物标志物NT - proBNP的水平降低,并且NT - proBNP水平与左心室面积分数变化(LVFAC)指数呈负相关,这使得NT - proBNP成为评估动物模型中细胞治疗疗效以及临床试验中前瞻性评估疗效的有吸引力的工具。
获得的结果表明,移植的SkMCs对心脏再生发挥了有益作用,并能够抑制LVR,这在分子水平上得到了证实,为监测MI新型细胞疗法的新方法带来了希望。