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Construction of vascularized pacemaker tissues by seeding cardiac progenitor cells and endothelial progenitor cells into Matrigel

机译:通过将心脏祖细胞和内皮祖细胞播种到Matrigel的血管化起搏器组织

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Abstract Aims Transplantation of a tissue engineered cardiac pacemaker (TECP) may represent a novel therapy for cardiac sinus node dysfunction. We previously reported that cardiac progenitor cells (CPCs) derived from embryonic heart tubes could differentiate into cardiac pacemaking cells after endothelin-1 treatment. We aimed to examine the feasibility of TECP fabricated from CPCs-derived pacemaking cells and vascularization of TECP fabricated from CPCs-derived pacemaking cells and endothelial progenitor cells (EPCs) in vitro and in vivo implantation. Main methods TECP created using CPCs-derived pacemaking cells and vTECP created by mixing CPCs and EPCs in vitro were implanted into rat hearts. Sinus node damaged was induced by formaldehyde insult. Key results Spontaneous beating tissues, namely TECP, were obtained after seeding CPCs-derived pacemaking cells into Matrigel. ECG and epicardial multielectrode array (MEA) measurements confirmed implanted TECP have electrical activity. TECP implantation promoted individual survival in sinus node damage models (15/22 animals lived versus 0/17 control). vTECP fabricated by mixing the both EPCs and CPCs-derived pacemaking cells with Matrigel in equal proportions optimally formed pre-vascularization in vitro . The implantation of vTECP enhanced electrical activity in vivo , which may correlate with increased vascularization. PI3K-Akt-VEGF/VEGFR signaling was involved with vascular ingrowth in vTECP. Significance Our data supports the therapeutic potential of TECP fabricated with the CPCs-derived pacemaking cells for sinus node dysfunction. Vascularization by the addition of EPCs is an important factor to sustain viability of the TECP in vivo .
机译:摘要旨在组织工程心脏起搏器(TECP)的移植可以代表心脏窦节点功能障碍的新疗法。我们以前报道,衍生自胚胎心脏管的心脏祖细胞(CPC)可以在内皮素-1处理后分化为心脏起期悬浮细胞。我们的旨在探讨在体外和体内植入中由CPCS衍生的星形制作细胞和中医祖细胞(EPCS)制造的TECP制造的TECP和血管化的可行性。主要方法使用CPCS衍生的起飞杆细胞和通过将CPC和EPCS在体外混合产生的CPCS衍生的起飞细胞和VTECP创建的TECP被植入大鼠心中。鼻窦节点受损是通过甲醛侮辱引起的。将CPC衍生的起毛细胞播种到Matrigel之后,获得了自发性击打组织,即TECP的关键结果。 ECG和心外膜多电极阵列(MEA)测量确认植入TECP具有电活动。 TECP植入促进鼻窦节点损伤模型中的个体存活(15/22动物居住而不是0/17控制)。通过将EPC和CPCS衍生的起毛纤维制作电池与Matrigel混合在体外最佳地形成的前血管化预形成的比例中,通过将EPC和CPCS衍生的起飞杆细胞混合来制造。 VTECP的植入增强的体内电活性,其可以与血管化增加相关。 PI3K-AKT-VEGF / VEGFR信号传导涉及VTECP的血管内灌注。重要性我们的数据支持与CPCS衍生的起飞细胞制造的TECP的治疗潜力用于窦节节功能障碍。通过添加EPCS的血管化是维持体内TECP活力的重要因素。

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