Stable benefit of embryonic stem cell therapy in myocardial infarction
Stable benefit of embryonic stem cell therapy in myocardial infarction
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DOI：
10.1152/ajpheart.01247.2003
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发表时间：
2004-08-01
影响因子：
4.8
通讯作者：
Terzic, A
中科院分区：
文献类型：
--
作者：
Hodgson, DM;Behfar, A;Terzic, A
心肌梗死的常规治疗方法减缓疾病进展，但对修复没有显著贡献。因为它有重新发生心脏的能力。胚胎干细胞被认为是心肌再生的潜在来源，但关于其最终治疗价值的信息有限。我们用CGR8胚胎干细胞治疗梗死大鼠心脏，预先检查其致心性，连续探测左心室功能，并确定最终病理结果。干细胞传递产生新的胚胎干细胞来源的心肌细胞，与梗死区域内的宿主心肌结合。这导致在3周内功能获益，持续随访12周，包括对-肾上腺素能挑战的强烈肌力反应。干细胞来源的心肌细胞的整合与正常的心室结构，小疤痕相关。心肌坏死的迹象也会减少。相比之下，假药治疗的梗死心脏表现为心室腔扩张和动脉瘤形成，心室功能差，对β -肾上腺素能刺激缺乏反应。没有移植排斥异位心源性猝死的证据治疗后观察肿瘤形成。这些发现表明，胚胎干细胞通过在宿主心肌内分化。对梗死心脏的收缩功能和心室重构有稳定的有益影响。
Conventional therapies for myocardial infarction attenuate disease progression without contributing significantly to repair. Because of the capacity for de novo cardiogenesis. embryonic stem cells are considered a potential source for mvocardial regeneration, yet limited information is available on their ultimate therapeutic value. We treated infarcted rat hearts with CGR8 embryonic stem cells preexamined for cardiogenicity, serially probed left ventricular function, and determined final pathological outcome. Stem cell delivery generated new cardiomyocytes of embryonic stem cell origin that integrated with host myocardium within infarct regions. This resulted in a functional benefit within 3 wk that remained sustained over 12 wk of continuous follow-up and included a vigorous inotropic response to beta-adrenergic challenge. Integration of stem cell-derived cardiomyocytes was associated with normalized ventricular architecture, little scar. and a decrease in signs of myocardial necrosis. In contrast, sham-treated infarcted hearts exhibited ventricular cavity dilation and aneurysm formation, poor ventricular function, and a lack of response to beta-adrenergic stimulation. No evidence of graft rejection, ectopy, sudden cardiac death. or tumor formation was observed after therapy. These findings indicate that embryonic stem cells, through differentiation within the host myocardium. can contribute to a stable beneficial outcome on contractile function and ventricular remodeling in the infarcted heart.