Sympathetic innervation induced in engrafted engineered cardiomyocyte sheets by glial cell line derived neurotrophic factor in vivo.

Sympathetic innervation induced in engrafted engineered cardiomyocyte sheets by glial cell line derived neurotrophic factor in vivo.
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DOI:
10.1155/2013/532720
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发表时间:
2013
影响因子:
--
通讯作者:
Ueda Y
Ueda Y
中科院分区:
生物学3区
文献类型:
--
作者:
Fu XM;Lee JK;Miwa K;Shimizu T;Takagishi Y;Hirabayashi M;Watabe K;Usui A;Kodama I;Ueda Y

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心肌组织工程的目的是利用工程化的心肌组织修复或再生受损的心肌。然而,这种策略受到移植物与天然心肌缺乏功能整合的阻碍。自主神经支配可能是移植物与宿主心肌正常功能的关键。在这项研究中,我们探讨了在体内诱导自主神经支配的工程心肌组织使用基因调控的腺病毒编码的胶质细胞源性神经营养因子(GDNF)的可行性。将转GFP基因(对照组)或GDNF过表达(GDNF组)的工程化心肌细胞片移植到大鼠冷冻损伤的心脏上。术后1、2、4周行免疫组织化学染色观察移植物中神经纤维的变化。对照组术后2周和GDNF组术后1周移植物中首次检测到生长相关蛋白43阳性神经和酪氨酸羟化酶阳性交感神经。GDNF组移植物中生长神经和交感神经密度明显增加。在移植物中未观察到胆碱乙酰转移酶免疫阳性的副交感神经。总之,GDNF可以有效地诱导交感神经支配到移植的工程化心肌细胞片层中。
The aim of myocardial tissue engineering is to repair or regenerate damaged myocardium with engineered cardiac tissue. However, this strategy has been hampered by lack of functional integration of grafts with native myocardium. Autonomic innervation may be crucial for grafts to function properly with host myocardium. In this study, we explored the feasibility of in vivo induction of autonomic innervation to engineered myocardial tissue using genetic modulation by adenovirus encoding glial cell line derived neurotrophic factor (GDNF). GFP-transgene (control group) or GDNF overexpressing (GDNF group) engineered cardiomyocyte sheets were transplanted on cryoinjured hearts in rats. Nerve fibers in the grafts were examined by immunohistochemistry at 1, 2, and 4 weeks postoperatively. Growth associated protein-43 positive growing nerves and tyrosine hydroxylase positive sympathetic nerves were first detected in the grafts at 2 weeks postoperatively in control group and 1 week in GDNF group. The densities of growing nerve and sympathetic nerve in grafts were significantly increased in GDNF group. No choline acetyltransferase immunopositive parasympathetic nerves were observed in grafts. In conclusion, sympathetic innervation could be effectively induced into engrafted engineered cardiomyocyte sheets using GDNF.
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