Cardiac progenitor cells and biotinylated insulin-like growth factor-1 nanofibers improve endogenous and exogenous myocardial regeneration after infarction.
Cardiac progenitor cells and biotinylated insulin-like growth factor-1 nanofibers improve endogenous and exogenous myocardial regeneration after infarction.
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DOI：
10.1161/circulationaha.109.852285
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发表时间：
2009-09-08
期刊：
影响因子：
37.8
通讯作者：
Kajstura J
中科院分区：
文献类型：
--
作者：
Padin-Iruegas ME;Misao Y;Davis ME;Segers VF;Esposito G;Tokunou T;Urbanek K;Hosoda T;Rota M;Anversa P;Leri A;Lee RT;Kajstura J
心脏祖细胞（CPC）具有IGF-1-IGF-1受体系统，并且IGF-1可以被拴系到自组装肽纳米纤维（NF-IGF-1），导致该生长因子向心肌的延长释放。因此，我们测试了局部注射克隆原性CPC和NF-IGF-1是否增强递送的和驻留的CPC的活化和分化，从而增强梗死后的心脏修复。在大鼠中诱导心肌梗死，并分析未处理的梗死和仅用CPC或NF-IGF-1处理的梗死，以及CPC和NF-IGF-1一起处理的梗死。对于单独暴露于CPC或NF-IGF-1的梗死，联合治疗导致左心室质量与腔室容积比更大增加，并且更好地保留+dP/dt、-dP/dt、射血分数和舒张壁应力。在所有治疗的梗死中检测到心肌再生，但联合治疗的新形成的心肌细胞的数量分别比CPC和NF-IGF-1高32%和230%。再生肌细胞体积的相应差异为48%和115%。类似地，具有CPC和NF-IGF-1的新形成的冠状小动脉的长度密度分别比单独具有CPC和NF-IGF-1的冠状小动脉的长度密度大73%和83%。重要的是，激活常驻CPC的旁分泌效应有助于心肌和血管发生。总的来说，CPC和NF-IGF-1治疗比CPC和NF-IGF-1单独治疗更能减少梗死面积。纳米纤维介导的IGF-1递送加入CPC治疗部分改善了梗死后心肌结构和功能的恢复。
Cardiac progenitor cells (CPCs) possess the IGF-1-IGF-1 receptor system and IGF-1 can be tethered to self-assembling peptide nanofibers (NF-IGF-1) leading to prolonged release of this growth factor to the myocardium. Therefore, we tested whether local injection of clonogenic CPCs and NF-IGF-1 potentiate the activation and differentiation of delivered and resident CPCs enhancing cardiac repair after infarction. Myocardial infarction was induced in rats, and untreated infarcts and infarcts treated with CPCs or NF-IGF-1 only, and CPCs and NF-IGF-1 together were analyzed. With respect to infarcts exposed to CPCs or NF-IGF-1 alone, combination therapy resulted in a greater increase in left ventricular mass-to-chamber volume ratio, and a better preservation of +dP/dt, −dP/dt, ejection fraction and diastolic wall stress. Myocardial regeneration was detected in all treated infarcts, but the number of newly formed myocytes with combination therapy was 32% and 230% higher than with CPCs and NF-IGF-1, respectively. Corresponding differences in the volume of regenerated myocytes were 48% and 115%. Similarly, the length density of newly formed coronary arterioles with both CPCs and NF-IGF-1 was 73% and 83% greater than with CPCs and NF-IGF-1 alone, respectively. Importantly, activation of resident CPCs by paracrine effects contributed to cardiomyogenesis and vasculogenesis. Collectively, CPCs and NF-IGF-1 therapy reduced infarct size more than CPCs and NF-IGF-1 alone. The addition of nanofiber-mediated IGF-1-delivery to CPC therapy improved partly the recovery of myocardial structure and function after infarction.