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干细胞效应的机制:磁共振成像的见解

Mechanisms of stem cell effects: insights from MRI.

作者信息

Rokosh G, Ghafghazi S, Bolli R

机构信息

Cardiovascular Medicine, University of Louisville, Louisville, KY, USA -

出版信息

Minerva Cardioangiol. 2013 Dec;61(6):605-16.

PMID:24253454
Abstract

Early results from stem cell trials to treat myocardial infarction have shown promise. Several types of stem cells have moved through phase I trials to demonstrate safety and some at the same time have shown significant potential for myocardial regeneration and functional recovery. The means by which stem cells contribute to improving myocardial function, however, remains unknown. Challenges in labeling stem cells for tracking and fate determination after cell transplantation have precluded establishing whether transplanted stem cell engraftment, expansion after engraftment, endogenous stem cell activation or a combination of these mechanisms contribute to improved function. Cardiac magnetic resonance imaging (cMRI), due to its inherent capabilities, has emerged as the imaging modality of choice to provide important insights into remodeling of myocardium after stem cell transplantation and its consequences on cardiac function. Of cMRI capabilities, excellent spatial resolution is instrumental in assessment of global and regional function and feasibility of scar quantification sets it apart from other imaging modalities and facilitates critical analysis. These capabilities permit the identification of dysfunctional myocardium and scar and changes in these regions over time. The effect of stem cell therapeutics on dysfunctional myocardium and scar can then be highlighted in longitudinal assessment in clinical trials. This has been demonstrated in the inaugural Phase I SCIPIO trial where patients received autologous C-kitPos cardiac stem cell (CSC) transplantation. Although the global function improved significantly with CSC transplantation, regional/segmental analysis provided crucial insights into the effects of CSCs on the most dysfunctional myocardial segments. Magnetic resonance imaging is also a contending and complementing modality in molecular imaging essential for mechanistic studies.

摘要

干细胞治疗心肌梗死的早期结果已显示出前景。几种类型的干细胞已通过一期试验以证明安全性,并且其中一些同时已显示出心肌再生和功能恢复的巨大潜力。然而,干细胞改善心肌功能的方式仍不明确。在细胞移植后对干细胞进行标记以追踪和确定其命运方面存在挑战,这使得无法确定移植的干细胞植入、植入后扩增、内源性干细胞激活或这些机制的组合是否有助于功能改善。心脏磁共振成像(cMRI)因其固有的能力,已成为首选的成像方式,可提供有关干细胞移植后心肌重塑及其对心脏功能影响的重要见解。在cMRI的各项能力中,出色的空间分辨率有助于评估整体和局部功能,而瘢痕定量的可行性使其有别于其他成像方式,并便于进行关键分析。这些能力能够识别功能失调的心肌和瘢痕以及这些区域随时间的变化。然后,在临床试验的纵向评估中可以突出干细胞疗法对功能失调心肌和瘢痕的影响。这在首个一期SCIPIO试验中得到了证明,该试验中患者接受了自体C-kit阳性心脏干细胞(CSC)移植。尽管CSC移植后整体功能显著改善,但区域/节段分析为了解CSC对功能最失调的心肌节段的影响提供了关键见解。磁共振成像也是分子成像中用于机制研究的一种有竞争力的补充方式。

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