Implantation of mouse embryonic stem cell-derived cardiac progenitor cells preserves function of infarcted murine hearts.

Implantation of mouse embryonic stem cell-derived cardiac progenitor cells preserves function of infarcted murine hearts.
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DOI:
10.1371/journal.pone.0011536
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发表时间:
2010-07-12
期刊:
影响因子:
3.7
通讯作者:
Gearhart JD
Gearhart JD
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Christoforou N;Oskouei BN;Esteso P;Hill CM;Zimmet JM;Bian W;Bursac N;Leong KW;Hare JM;Gearhart JD

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干细胞移植在心肌梗死损伤的治疗中具有广阔的应用前景。我们最近描述了胚胎干细胞衍生的心脏祖细胞(cpc)能够分化为心肌细胞、血管内皮和平滑肌。在这项研究中,我们假设移植的心肌细胞将通过参与肌肉替代和新生血管来保持梗死心脏的功能。分化的心肌细胞在体外与心肌细胞形成功能性机电连接,并在厘米尺度上传导动作电位。当移植到梗死小鼠心脏时,CPCs在梗死区和周围心肌长期植入,未引起畸胎瘤或心律失常。移植物细胞分化为交叉纹心肌细胞,与宿主细胞形成间隙连接,同时也有助于新生血管的形成。连续超声心动图和压力-容量导管检查显示心室扩张减弱,左心室分数缩短、收缩和舒张功能保持不变。我们的研究结果表明,CPCs可以移植、分化并保留梗死心脏的功能输出。
Stem cell transplantation holds great promise for the treatment of myocardial infarction injury. We recently described the embryonic stem cell-derived cardiac progenitor cells (CPCs) capable of differentiating into cardiomyocytes, vascular endothelium, and smooth muscle. In this study, we hypothesized that transplanted CPCs will preserve function of the infarcted heart by participating in both muscle replacement and neovascularization. Differentiated CPCs formed functional electromechanical junctions with cardiomyocytes in vitro and conducted action potentials over cm-scale distances. When transplanted into infarcted mouse hearts, CPCs engrafted long-term in the infarct zone and surrounding myocardium without causing teratomas or arrhythmias. The grafted cells differentiated into cross-striated cardiomyocytes forming gap junctions with the host cells, while also contributing to neovascularization. Serial echocardiography and pressure-volume catheterization demonstrated attenuated ventricular dilatation and preserved left ventricular fractional shortening, systolic and diastolic function. Our results demonstrate that CPCs can engraft, differentiate, and preserve the functional output of the infarcted heart.
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