Stem cells provide a new strategy for the treatment of cardiac diseases; however, their effectiveness in dilated cardiomyopathy (DCM) has not been investigated. In this study, cardiosphere-derived cells (CDCs) were isolated from infants (≤ 24 months) and identified by the cell surface markers CD105, CD90, CD117 and CD45, which is consistent with a previous report, although increased CD34 expression was observed. The molecular expression profile of CDCs from infants was determined by RNA sequencing and compared with adult CDCs, showing that infant CDCs have almost completely altered gene expression patterns compared with adult CDCs. The upregulated genes in infant CDCs are mainly related to the biological processes of cell morphogenesis and differentiation. The molecular profile of infant CDCs was characterized by lower expression of inflammatory cytokines and higher expression of stem cell markers and growth factors compared to adult CDCs. After intramyocardial administration of infant CDCs in the heart of DCM rats, we found that infant CDCs remained in the heart of DCM rats for at least 7 days, improved DCM-induced cardiac function impairment and protected the myocardium by elevating the left ventricular ejection fraction and fraction shortening. However, the effectiveness of transplanted CDCs was reversed later, as increased fibrosis formation instead of angiogenesis was observed. We concluded that infant CDCs, with higher expression of stem cell markers and growth factors, exhibit non-durable heart protection due to limited residence time in the heart of DCM animals, suggesting that multiple administrations of the CDCs or post-regulation after transplantation may be the key for cell therapy in the future.

中文翻译：

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婴儿心球来源的细胞在扩张型心肌病大鼠中显示出非持久的心脏保护作用。

干细胞为心脏病的治疗提供了新的策略。但是，尚未研究其在扩张型心肌病（DCM）中的有效性。在这项研究中，从婴儿（≤24个月）分离了心球来源的细胞（CDC），并通过细胞表面标记CD105，CD90，CD117和CD45进行了鉴定，尽管观察到CD34表达增加，但与先前的报道一致。通过RNA测序确定了婴儿CDC的分子表达谱，并与成人CDC进行了比较，表明婴儿CDC与成人CDC相比几乎完全改变了基因表达模式。婴儿CDCs中的上调基因主要与细胞形态发生和分化的生物学过程有关。婴儿CDC的分子特征是与成人CDC相比，炎症细胞因子的表达较低，而干细胞标志物和生长因子的表达较高。在DCM大鼠心脏内对婴儿CDC进行心肌内给药后，我们发现婴儿CDC在DCM大鼠心脏中保留了至少7天，改善了DCM引起的心脏功能损害，并通过提高左心室射血分数和心肌保护了心肌。分数缩短。然而，后来移植的CDC的有效性被逆转，因为观察到纤维化形成增加而不是血管生成。我们得出的结论是，由于干细胞标记物和生长因子的较高表达，婴儿CDC由于在DCM动物心脏中的停留时间有限而显示出非持久的心脏保护作用，