Optical mapping of cryoinjured rat myocardium grafted with mesenchymal stem cells
Optical mapping of cryoinjured rat myocardium grafted with mesenchymal stem cells
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DOI：
10.1152/ajpheart.00019.2011
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发表时间：
2012-01-01
影响因子：
4.8
通讯作者：
Laurita, Kenneth R.
中科院分区：
文献类型：
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作者：
Costa, Andrea R.;Panda, Nikhil C.;Laurita, Kenneth R.
科斯塔AR，熊猫NC，永S，马约加ME，帕洛夫斯基GP，范K，宾夕法尼亚MS，劳丽塔KR。移植间充质干细胞的冷冻损伤大鼠心肌的光学标测。Am J Physiol心脏圈Physiol 302：H270-H277,2012。2011年10月28日首次出版；doi：10.1152/ajpheart.00019.2011。-间充质干细胞(MSCs)已被证明在急性心肌梗死环境中应用时可以改善心脏电生理。然而，MSCs的电生理表型尚不清楚。我们假设，心肌内移植的MSCs可以植入冷冻损伤的心肌，但不会主动产生动作电位。在成年大鼠心脏左室心外膜表面形成冷冻损伤后的瘢痕。30min内注入生理盐水(n=11)或1，1‘-dioctadecyl-3，3，3，3’-tetramethyl-indocarbocyanine标记的骨髓间充质干细胞(2×10(6))(n=16)。3wk时，分别用光学标记法和细胞分离法测量细胞的光动作电位和钙瞬变。组织学分析证实心外膜下瘢痕厚度和表达连接蛋白-43的DII阳性细胞的存在。瘢痕内MSC阳性部位的光动作电位波幅(53.8+/-14.3%)高于无MSCs部位(35.3+/-14.2%，P<0.05)和假瘢痕内(33.5+/-6.9%，P<；0.05)。同时动作电位上行、消融相邻存活心肌后动作电位活动丧失、分离的DII+细胞无快速钙瞬变反应的证据表明，移植的MSCs的电生理影响是电紧性的。当MSCs直接注射到冷冻损伤处时，MSCs可以植入，并与动作电位活动的证据有关。然而，我们的结果表明，这种活动不是由于动作电位的产生，而是来自邻近存活心肌的消极影响。
Costa AR, Panda NC, Yong S, Mayorga ME, Pawlowski GP, Fan K, Penn MS, Laurita KR. Optical mapping of cryoinjured rat myocardium grafted with mesenchymal stem cells. Am J Physiol Heart Circ Physiol 302: H270-H277, 2012. First published October 28, 2011; doi: 10.1152/ajpheart.00019.2011.-Mesenchymal stem cells (MSCs) have been shown to improve cardiac electrophysiology when administered in the setting of acute myocardial infarction. However, the electrophysiological phenotype of MSCs in situ is not clear. We hypothesize that MSCs delivered intramyocardially to cryoinjured myocardium can engraft, but will not actively generate, action potentials. Cryoinjury-induced scar was created on the left ventricular epicardial surface of adult rat hearts. Within 30 min, hearts were injected with saline (sham, n = 11) or bone marrow-derived MSCs (2 x 10(6)) labeled with 1,1'-dioctadecyl-3,3,3,3'-tetramethyl-indocarbocyanine percholate (DiI; n = 16). At 3 wk, optical mapping and cell isolation were used to measure optical action potentials and calcium transients, respectively. Histological analysis confirmed subepicardial scar thickness and the presence of DiI-positive cells that express connexin-43. Optical action potential amplitude within the scar at MSC-positive sites (53.8 +/- 14.3%) was larger compared with sites devoid of MSCs (35.3 +/- 14.2%, P < 0.05) and sites within the scar of shams (33.5 +/- 6.9%, P < 0.05). Evidence of simultaneous action potential upstroke, the loss of action potential activity following ablation of adjacent viable myocardium, and no rapid calcium transient response in isolated DiI + cells suggest that the electrophysiological influence of engrafted MSCs is electrotonic. MSCs can engraft when directly injected into a cryoinjury and are associated with evidence of action potential activity. However, our results suggest that this activity is not due to generation of action potentials, but rather passive influence coupled from neighboring viable myocardium.