Sympathetic innervation induced in engrafted engineered cardiomyocyte sheets by glial cell line derived neurotrophic factor in vivo.
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.
Department of Cardiac Surgery, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Xian-ming
XM
Fu
Jong-Kook
JK
Lee
Keiko
K
Miwa
Tatsuya
T
Shimizu
Yoshiko
Y
Takagishi
Masumi
M
Hirabayashi
Kazuhiko
K
Watabe
Akihiko
A
Usui
Itsuo
I
Kodama
Yuichi
Y
Ueda
D000256:Adenoviridae; D000818:Animals; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics*; D006321:Heart / Q000294:innervation*; D016027:Heart Transplantation; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000637:transplantation; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D051381:Rats; D013564:Sympathetic Nervous System / Q000254:growth & development / Q000601:surgery; D023822:Tissue Engineering; D019737:Transplants / Q000254:growth & development / Q000294:innervation
D051100:Glial Cell Line-Derived Neurotrophic Factor