CCND2 Overexpression Enhances the Regenerative Potency of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Remuscularization of Injured Ventricle.
CCND2 Overexpression Enhances the Regenerative Potency of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Remuscularization of Injured Ventricle.
复制标题
CCND2 过表达增强人诱导多能干细胞来源的心肌细胞的再生能力：受损心室的肌重化。
DOI：
10.1161/circresaha.117.311504
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发表时间：
2018-01-05
影响因子：
20.1
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Zhu W;Zhao M;Mattapally S;Chen S;Zhang J
The effectiveness of transplanted, human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) for treatment of ischemic myocardial injury is limited by the exceptionally low engraftment rate. To determine whether overexpression of the cell-cycle activator CCND2 in hiPSC-CMs can increase the graft size and improve myocardial recovery in a mouse model of myocardial infarction (MI) by increasing the proliferation of grafted cells. Human CCND2 was delivered to hiPSCs via lenti-viral mediated gene transfection. In cultured cells, markers for cell-cycle activation and proliferation were ~3–7 folds higher in CCND2-overexpressing hiPSC-CMs (hiPSC-CCND2OECMs) than in hiPSC-CMs with normal levels of CCND2 (hiPSC-CCND2WTCMs) (p<0.01). The pluripotent genes (Oct 4, Sox2, Nanog) decrease to minimal- and undetectable -levels at day 1 and 10 after differentiate to CMs. In the mouse MI model, cardiac function, infarct size, and the number of engrafted cells were similar at week 1 after treatment with hiPSC-CCND2OECMs or hiPSC-CCND2WTCMs but was about tripled in hiPSC-CCND2OECM–treated than in hiPSC-CCND2WTCM–treated animals at week 4 (p<0.01). The cardiac function and infarct size were significantly better in both cell-treatment groups hearts than in control hearts, which was most prominent in hiPSC-CCND2OECM–treated animals (p<0.05, each). No tumor formation was observed in any hearts. CCND2 overexpression activates cell-cycle progression in hiPSC-CMs that results in a significant enhanced potency for myocardial repair as evidenced by remuscularization of injured myocardium. This LV muscle regeneration and increased angiogenesis in border zone are accompanied by a significant improvement of LV chamber function.
