Therapeutic efficacy of cardiosphere-derived cells in a transgenic mouse model of non-ischaemic dilated cardiomyopathy
Therapeutic efficacy of cardiosphere-derived cells in a transgenic mouse model of non-ischaemic dilated cardiomyopathy
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DOI：
10.1093/eurheartj/ehu196
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发表时间：
2015-03-21
影响因子：
39.3
通讯作者：
Marban, Eduardo
中科院分区：
文献类型：
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作者：
Aminzadeh, Mohammad A.;Tseliou, Eleni;Marban, Eduardo
目的心脏球源性细胞(CDCs)在心肌梗死后发挥再生作用。然而，CDC在非缺血性扩张型心肌病(DCM)中是否有益尚不清楚。我们测试了CDC移植对心脏特异性GαQ过度表达的小鼠的影响，这些小鼠可预测发生心脏进行性扩张和衰竭，并加速死亡。方法和结果将野生型小鼠CDC(10(5)细胞)或赋形剂仅注射到6、8和11周龄的GαQ小鼠的心肌内。接受赋形剂治疗的小鼠在3个月的随访中心脏功能恶化，伴随着氧化应激、炎症和不利的心室重构。相比之下，CDCs保留了心脏功能和容量，提高了存活率，促进了心肌生成，同时钝化了GαQ诱导的心脏氧化应激和炎症。这种益处的机制是间接的，因为移植细胞的长期植入率极低。结论心肌球源性细胞逆转了细胞信号转导的基本异常，防止了不利的重构，并提高了DCM小鼠模型的存活率。对非缺血性心力衰竭的疾病进展有积极影响的能力预示着疾病预防控制中心的新的潜在治疗应用。
Aim Cardiosphere-derived cells (CDCs) produce regenerative effects in the post-infarct setting. However, it is unclear whether CDCs are beneficial in non-ischaemic dilated cardiomyopathy (DCM). We tested the effects of CDC transplantation in mice with cardiac-specific G alpha q overexpression, which predictably develop progressive cardiac dilation and failure, with accelerated mortality.Methods and Results Wild-type mouse CDCs (10(5) cells) or vehicle only were injected intramyocardially in 6-, 8-, and 11-week-old G alpha q mice. Cardiac function deteriorated in vehicle-treated mice over 3 months of follow-up, accompanied by oxidative stress, inflammation and adverse ventricular remodelling. In contrast, CDCs preserved cardiac function and volumes, improved survival, and promoted cardiomyogenesis while blunting G alpha q-induced oxidative stress and inflammation in the heart. The mechanism of benefit is indirect, as long-term engraftment of transplanted cells is vanishingly low.Conclusions Cardiosphere-derived cells reverse fundamental abnormalities in cell signalling, prevent adverse remodelling, and improve survival in a mouse model of DCM. The ability to impact favourably on disease progression in non-ischaemic heart failure heralds new potential therapeutic applications of CDCs.