Human cardiosphere-derived cells from advanced heart failure patients exhibit augmented functional potency in myocardial repair.
Human cardiosphere-derived cells from advanced heart failure patients exhibit augmented functional potency in myocardial repair.
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DOI：
10.1016/j.jchf.2013.08.008
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发表时间：
2014-02
期刊：
影响因子：
--
通讯作者：
Marbán E
中科院分区：
文献类型：
--
作者：
Cheng K;Malliaras K;Smith RR;Shen D;Sun B;Blusztajn A;Xie Y;Ibrahim A;Aminzadeh MA;Liu W;Li TS;De Robertis MA;Marbán L;Czer LSC;Trento A;Marbán E
这项研究试图比较来自健康和患病人类心脏的细胞的再生能力。临床前研究和CADUCEUS（心球源性自体干细胞逆转心室功能障碍）试验的结果支持这样一种观点，即来自正常和最近梗死的心脏的心球源性细胞（cdc）能够在心肌梗死（MI）后再生健康的心脏组织。目前尚不清楚来自晚期心力衰竭（HF）患者的cdc是否具有相同的再生能力。在急性心肌梗死小鼠模型中，我们比较了三组CDCs的再生潜力和功能益处：1)非衰竭（NF）供体心脏：移植后健康供体心脏；2)心肌梗死：活检前9 ~ 35天有心肌梗死的患者；3) HF：心脏移植移植的晚期心肌病组织。3组细胞生长和表型相同。注射HF cdc对小鼠的治疗效果最大，治疗后3周左心室射血分数最高，梗死壁最厚，组织存活最多，瘢痕最少。体外实验显示，HF CDCs分泌更高水平的基质细胞衍生因子1 (SDF-1)，这可能有助于增强细胞对氧化应激的抵抗力，增强血管生成，提高心肌细胞存活率。组织学分析表明，HF CDCs移植效果更好，招募了更多的内源性干细胞，诱导了更多的血管生成和心肌细胞周期再进入。在自体CDCs治疗的CADUCEUS患者中，随着时间的推移，cdc分泌的SDF-1水平与疤痕质量的减少相关。晚期HF患者的cdc在改善心肌梗死后心室功能障碍方面表现出增强的效力，可能是通过sdf -1介导的机制。
This study sought to compare the regenerative potency of cells derived from healthy and diseased human hearts. Results from pre-clinical studies and the CADUCEUS (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction) trial support the notion that cardiosphere-derived cells (CDCs) from normal and recently infarcted hearts are capable of regenerating healthy heart tissue after myocardial infarction (MI). It is unknown whether CDCs derived from advanced heart failure (HF) patients retain the same regenerative potency. In a mouse model of acute MI, we compared the regenerative potential and functional benefits of CDCs derived from 3 groups: 1) non-failing (NF) donor: healthy donor hearts post-transplantation; 2) MI: patients who had an MI 9 to 35 days before biopsy; and 3) HF: advanced cardiomyopathy tissue explanted at cardiac transplantation. Cell growth and phenotype were identical in all 3 groups. Injection of HF CDCs led to the greatest therapeutic benefit in mice, with the highest left ventricular ejection fraction, thickest infarct wall, most viable tissue, and least scar 3 weeks after treatment. In vitro assays revealed that HF CDCs secreted higher levels of stromal cell-derived factor 1 (SDF-1), which may contribute to the cells’ augmented resistance to oxidative stress, enhanced angiogenesis, and improved myocyte survival. Histological analysis indicated that HF CDCs engrafted better, recruited more endogenous stem cells, and induced greater angiogenesis and cardiomyocyte cell-cycle re-entry. CDC-secreted SDF-1 levels correlated with decreases in scar mass over time in CADUCEUS patients treated with autologous CDCs. CDCs from advanced HF patients exhibit augmented potency in ameliorating ventricular dysfunction post-MI, possibly through SDF-1–mediated mechanisms.
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影响因子：
3.7
作者：
Davis DR;Zhang Y;Smith RR;Cheng K;Terrovitis J;Malliaras K;Li TS;White A;Makkar R;Marbán E
通讯作者：
Marbán E
影响因子：
14
作者：
Cheng, Ke;Shen, Deliang;Smith, Jeremy;Galang, Giselle;Sun, Baiming;Zhang, Jinying;Marban, Eduardo
通讯作者：
Marban, Eduardo
心力衰竭患者的循环干细胞随 NYHA 分期的不同而变化。
影响因子：
5.3
作者：
Fortini C;Toffoletto B;Fucili A;Puppato E;Olivares A;Beltrami AP;Fiorelli V;Bergamin N;Cesselli D;Morelli C;Francolini G;Ferrari R;Beltrami CA
通讯作者：
Beltrami CA
影响因子：
5.2
作者：
Li, Tao-Sheng;Cheng, Ke;Lee, Shuo-Tsan;Matsushita, Satoshi;Davis, Darryl;Malliaras, Konstantinos;Zhang, Yiqiang;Matsushita, Noriko;Smith, Rachel Ruckdeschel;Marban, Eduardo
通讯作者：
Marban, Eduardo
影响因子：
5.2
作者：
Guo, Y;Hangoc, G;Broxmeyer, HE
通讯作者：
Broxmeyer, HE