Multimodality noninvasive imaging demonstrates in vivo cardiac regeneration after mesenchymal stem cell therapy
Multimodality noninvasive imaging demonstrates in vivo cardiac regeneration after mesenchymal stem cell therapy
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DOI：
10.1016/j.jacc.2006.06.073
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发表时间：
2006-11-21
影响因子：
24
通讯作者：
Hare, Joshua M.
中科院分区：
文献类型：
--
作者：
Amado, Luciano C.;Schuleri, Karl H.;Hare, Joshua M.
本研究的目的是用非侵入性多模态成像来检验同种异体间充质干细胞（MSC）在心肌梗死（MI）后体内产生和/或刺激主动心脏再生的假设。这种现象背后的机制还不完全清楚。方法我们采用磁共振成像（MRI）和多探测器计算机断层扫描（MDCT）成像在MSC治疗的猪（n = 10）和对照组（n = 12）在前壁心肌梗死后连续观察2个月。用MDCT显示的组织的亚内膜边缘，用MRI标记评估区域收缩。测量大体病理标本的边缘厚度，以证实MDCT成像的结果，并测量心肌细胞在内膜下边缘和非梗死区的大小。结果多层螺旋CT显示，MSC治疗的动物梗死区内膜下存活心肌厚度增加（MI后1周和8周，分别为1.0 +/- 0.2 mm至2.0 +/- 0.3 mm，p = 0.028，n = 4），梗死瘢痕相应减少（5.1 +/- 0.5 mm至3.6 +/- 0.2 mm，p = 0.044）。对照受试者（n = 4）未发生变化。标记MRI显示主动收缩力的时间依赖性恢复与新组织外观平行。该边缘由形态学正常的心肌细胞组成，MSC治疗组的心肌细胞比对照组小（11.6 +/-0.2 μ m vs.12.6 +/- 0.2 μ m，p < 0.05）。这些数据与再生过程一致，突出了无创多模态成像评估心肌再生策略的结构和功能基础的价值，并具有潜在的临床应用。
OBJECTIVES The purpose of this study was to test the hypothesis, with noninvasive multimodality imaging, that allogeneic mesenchymal stem cells (MSCs) produce and/or stimulate active cardiac regeneration in vivo after myocardial infarction (MI).BACKGROUND Although intramyocardial injection of allogeneic MSCs improves global cardiac function after MI, the mechanism(s) underlying this phenomenon are incompletely understood.METHODS We employed magnetic resonance imaging (MRI) and multi-detector computed tomography (MDCT) imaging in MSC-treated pigs (n = 10) and control subjects (n = 12) serially for a 2-month period after anterior MI. A sub-endocardial rim of tissue, demonstrated with MDCT, was assessed for regional contraction with MRI tagging. Rim thickness was also measured on gross pathological specimens, to confirm the findings of the MDCT imaging, and the size of cardiomyocytes was measured in the sub-endocardial rim and the non-infarct zone.RESULTS Multi-detector computed tomography demonstrated increasing thickness of sub-endocardial viable myocardium in the infarct zone in MSC-treated animals (1.0 +/- 0.2 mm to 2.0 +/- 0.3 mm, 1 and 8 weeks after MI, respectively, p = 0.028, n = 4) and a corresponding reduction in infaret scar (5.1 +/- 0.5 mm to 3.6 +/- 0.2 mm, p = 0.044). No changes occurred in control subjects (n = 4). Tagging MRI demonstrated time-dependent recovery of active contractility paralleling new tissue appearance. This rim was composed of morphologically normal cardiomyocytes, which were smaller in MSC-treated versus control subjects (11.6 +/- 0.2 mu m vs. 12.6 +/- 0.2 lim, p < 0.05).CONCLUSIONS With serially obtained MRI and MDCT, we demonstrate in vivo reappearance of myocardial tissue in the MI zone accompanied by time-dependent restoration of contractile function. These data are consistent with a regenerative process, highlight the value of noninvasive multimodality imaging to assess the structural and functional basis for myocardial regenerative strategies, and have potential clinical applications.