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

Xian Ming Fu, Jong Kook Lee, Keiko Miwa, Tatsuya Shimizu, Yoshiko Takagishi, Masumi Hirabayashi, Kazuhiko Watabe, Akihiko Usui, Itsuo Kodama, Yuichi Ueda

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number532720
JournalBioMed Research International
Volume2013
DOIs
Publication statusPublished - 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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