title: Survival and function of mouse embryonic stem cell-derived cardiomyocytes in ectopic transplants.
abstract: OBJECTIVE
  Embryonic stem cell-derived cardiomyocytes are a useful source for cell transplantation into the heart, as well as for tissue engineering of the extracardiac vascular system. The present study was designed to investigate the survival and contractile function of embryonic stem cell-derived cardiomyocytes around large blood vessels to assess the feasibility of their ectopic use for future engineering of cardiovascular tissues.
  
  
  METHODS
  The mouse embryonic stem cell-derived cardiomyocytes were transplanted into the retroperitoneum of the adult nude mice, and the myocardial tissues that developed were characterized by electrophysiological and histological techniques.
  
  
  RESULTS
  Macroscopic and electrophysiological analyses showed spontaneously contracting transplants in the host retroperitoneum 7 and 30 days after transplantation. Immunohistochemistry detected developing cardiomyocytes in the transplants on Day 7, which formed the myocardial tissues. They were positive for cardiac troponin I, cadherin, connexin 43, and proliferating cell nuclear antigen, but negative for alpha-smooth muscle actin. Vascular formation was discernible in the transplant tissues. By Day 30, more mature myocardial tissues had been established in the transplants. Electron microscopic study emphasized that the transplant tissues comprised cardiomyocytes, in which myofibrils with organized sarcomeres were observed. Desmosomes, fasciae adherens and gap junctions were evident in the cellular junctions.
  
  
  CONCLUSIONS
  The cardiomyocytes derived from the mouse ES cells were demonstrated to be viable and function in the ectopic site of the host retroperitoneum up to Day 30, following a process of proliferation and differentiation. Vascularization and host perfusion beneficial for the survival of the cardiomyocytes occurred in the transplants.
authors.affiliation: Department of Anatomy and Organ Technology, Shinshu University School of Medicine, 3-1-1 Asahi, 390-8621, Matsumoto, Japan. kohei@sch.md.shinshu-u.ac.jp
authors.forename: Kohei
authors.initials: K
authors.lastname: Johkura
authors.forename: Li
authors.initials: L
authors.lastname: Cui
authors.forename: Akihiro
authors.initials: A
authors.lastname: Suzuki
authors.forename: Ruifeng
authors.initials: R
authors.lastname: Teng
authors.forename: Akiko
authors.initials: A
authors.lastname: Kamiyoshi
authors.forename: Shintaro
authors.initials: S
authors.lastname: Okamura
authors.forename: Suguru
authors.initials: S
authors.lastname: Kubota
authors.forename: Xu
authors.initials: X
authors.lastname: Zhao
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Asanuma
authors.forename: Yasumitsu
authors.initials: Y
authors.lastname: Okouchi
authors.forename: Naoko
authors.initials: N
authors.lastname: Ogiwara
authors.forename: Yoh ichi
authors.initials: Yi
authors.lastname: Tagawa
authors.forename: Katsunori
authors.initials: K
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001808:Blood Vessels; D015820:Cadherins / Q000032:analysis; D002454:Cell Differentiation; D002470:Cell Survival; D002828:Choristoma; D018031:Connexin 43 / Q000032:analysis; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008819:Mice, Nude; D008854:Microscopy, Electron; D023421:Models, Animal; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000648:ultrastructure; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous; D019210:Troponin I / Q000032:analysis
chemical_list: D015415:Biomarkers; D015820:Cadherins; D018031:Connexin 43; D018809:Proliferating Cell Nuclear Antigen; D019210:Troponin I