Transplantation of platelet gel spiked with cardiosphere-derived cells boosts structural and functional benefits relative to gel transplantation alone in rats with myocardial infarction.

Transplantation of platelet gel spiked with cardiosphere-derived cells boosts structural and functional benefits relative to gel transplantation alone in rats with myocardial infarction.
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DOI:
10.1016/j.biomaterials.2011.12.040
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发表时间:
2012-04
期刊:
影响因子:
14
通讯作者:
Marban, Eduardo
Marban, Eduardo
中科院分区:
工程技术1区
文献类型:
--
作者:
Cheng, Ke;Shen, Deliang;Smith, Jeremy;Galang, Giselle;Sun, Baiming;Zhang, Jinying;Marban, Eduardo

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新兴的干细胞治疗和生物材料领域已经开始为缺血性心肌病的治疗提供有希望的策略。已知血小板凝胶和心球衍生细胞(CDC)在心肌梗死(MI)后分别移植时是有益的。我们假设预先接种CDCs的血小板凝胶可以提高治疗效果。血小板凝胶和CDCs分别来自同系大鼠的静脉血和心脏活检。在体外,CDCs在血小板凝胶中培养的活力,生长和形态进行了表征。当递送到梗塞的大鼠心脏中时,预先接种有CDC的血小板凝胶比单独的血小板凝胶更有效地填充内源性心肌细胞和内皮细胞。在用具有CDC的凝胶处理的心脏中,内分泌c-kit阳性细胞的募集增强。在3周时,用CDC接种的血小板凝胶处理的心脏表现出不良左心室(LV)重构的最大衰减和最高的心脏功能(即,LV射血分数)与仅用凝胶或载体对照移植的心脏相比。组织学分析显示,尽管一些移植的CDC在受体心脏中分化为心肌细胞和内皮细胞,但大部分增量益处来自CDC介导的内源性修复。预先接种CDCs的血小板凝胶增强了生物材料治疗心肌梗死的功能获益。
The emerging field of stem cell therapy and biomaterials has begun to provide promising strategies for the treatment of ischemic cardiomyopathy. Platelet gel and cardiosphere-derived cells (CDCs) are known to be beneficial when transplanted separately post-myocardial infarction (MI). We hypothesize that pre-seeding platelet gel with CDCs can enhance therapeutic efficacy. Platelet gel and CDCs were derived from venous blood and heart biopsies of syngeneic rats, respectively. In vitro, the viability, growth, and morphology of CDCs cultured in platelet gel were characterized. When delivered into infarcted rat hearts, platelet gel pre-seeded with CDCs was more efficiently populated with endogenous cardiomyocytes and endothelial cells than platelet gel alone. Recruitment of endogeous c-kit positive cells was enhanced in the hearts treated with gel with CDC. At 3 weeks, the hearts treated with CDC-seeded platelet gel exhibited the greatest attenuation of adverse left ventricular (LV) remodeling and the highest cardiac function (i.e., LV ejection fraction) as compared to hearts transplanted with gel only or vehicle controls. Histological analysis revealed that, though some transplanted CDCs differentiated into cardiomyocytes and endothelial cells in the recipients’ hearts, most of the incremental benefit arose from CDC-mediated endogenous repair. Pre-seeding platelet gel with CDCs enhanced the functional benefit of biomaterial therapy for treating myocardial infarction.
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