| 摘要: |
| 目的将携带人超极化激活环核苷酸门控通道2(hHCN2)基因的自体间充质干细胞(MSCs)移植入完全性房室传导阻滞(CHB) 猪模型的希氏束中，探讨构建自体生物起搏器的可行性。方法构建包含hHCN2基因的重组腺病毒，转染猪MSCs。构建猪的CHB模型。将转基因的MSCs移植入希氏束后，观察其心率变化及对儿茶酚胺的反应性。对移植部位的心肌行组织学及免疫荧光检查。结果成功构建重组腺病毒 pAd.hHCN2并转染猪MSCs。自体移植于CHB动物模型希氏束后，与对照组相比，转基因 MSCs显著提升了实验组的心率(P<0.01)，且其心律具有儿茶酚胺反应性。移植部位心肌取样检查显示MSCs 在心肌中存活并且表达hHCN2蛋白。结论在猪CHB模型中，移植入希氏束的转hHCN2基因的自体 MSCs 短期内可以发挥生物起搏器的功能。 |
| 关键词: 间充质干细胞 人超极化激活环核苷酸门控通道2 自体移植 完全性房室传导阻滞 |
| DOI：10.3724/SP.J.1008.2011.0465 |
| 投稿时间：2010-12-22修订日期：2011-04-06 |
| 基金项目:国家自然科学基金(30672075,30700157). |
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| Autotransplantation of genetically-altered mesenchymal stem cells in treatment of complete heart block in porcine |
| LI Shu-chun,ZHANG Hao,DUAN Lian,GONG De-jun,YUAN Yang,XU Zhi-yun* |
| (Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China) |
| Abstract: |
| ObjectiveTo transplant the autologous mesenchymal stem cells(MSCs) carrying human hyperpolarization activated cyclic nucleotide gated channel 2 (hHCN2) gene into the His-bundle in porcine model of complete heart block (CHB), so as to assess the possibility of establishing autologous biological pacing. MethodsWe constructed the recombinant adenovirus containing hHCN2 gene to transfect the porcine MSCs. After autotransplantation into the His-bundle in CHB model, the genetically-altered MSCs were tested for their ability to provide a stable and catecholamine-responsive heart rhythm. Histological and immunofluorescence analyses were also performed for the myocardium of the injection site. ResultsRecombinant adenovirus pAd.hHCN2 was successfully constructed. Porcine MSCs were transfected by the adenovirus. After autotransplantation, transgenic MSCs significantly enhanced the heart rates in porcine CHB model compared with the control group (P<0.01), and the cardiac rhythms in the transgenic MSC group were catecholamine responsive. Tissues obtained from the transplanted heart sites showed that the MSCs survived in the myocardium and overexpressed hHCN2 protein. ConclusionTransplantation of autologous genetically-altered MSCs into the His-bundle in porcine CHB model can serve as a short-term catecholamine-responsive biological pacemaker. |
| Key words: mesenchymal stem cells human hyperpolarization activated cyclic nucleotide gated channel 2 |
