title: Enhanced survival of transplanted human induced pluripotent stem cell-derived cardiomyocytes by the combination of cell sheets with the pedicled omental flap technique in a porcine heart.
abstract: BACKGROUND
  Transplantation of cardiomyocytes that are derived from human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) shows promise in generating new functional myocardium in situ, whereas the survival and functionality of the transplanted cells are critical in considering this therapeutic impact. Cell-sheet method has been used to transplant many functional cells; however, potential ischemia might limit cell survival. The omentum, which is known to have rich vasculature, is expected to be a source of blood supply. We hypothesized that transplantation of hiPS-CM cell sheets combined with an omentum flap may deliver a large number of functional hiPS-CMs with enhanced blood supply.
  
  
  RESULTS
  Retrovirally established human iPS cells were treated with Wnt signaling molecules to induce cardiomyogenic differentiation, followed by superparamagnetic iron oxide labeling. Cell sheets were created from the magnetically labeled hiPS-CMs using temperature-responsive dishes and transplanted to porcine hearts with or without the omentum flap (n=8 each). Two months after transplantation, the survival of superparamagnetic iron oxide-labeled hiPS-CMs, assessed by MRI, was significantly greater in mini-pigs with the omentum than in those without it; histologically, vascular density in the transplanted area was significantly greater in mini-pigs with the omentum than in those without it. The transplanted tissues contained abundant cardiac troponin T-positive cells surrounded by vascular-rich structures.
  
  
  CONCLUSIONS
  The omentum flap enhanced the survival of hiPS-CMs after transplantation via increased angiogenesis, suggesting that this strategy is useful in clinical settings. The combination of hiPS-CMs and the omentum flap may be a promising technique for the development of tissue-engineered vascular-rich new myocardium in vivo.
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan (M.K., S.M., S.F., K.M., E.I., N.S., T.K., K.T., Y.S.); Medical Center for Translational Research, Osaka University Hospital, Suita, Osaka, Japan (A.S.); Department of Biostatistics, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan (T.D.); Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan (T.S., T.O.).
authors.forename: Masashi
authors.initials: M
authors.lastname: Kawamura
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyagawa
authors.forename: Satsuki
authors.initials: S
authors.lastname: Fukushima
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Saito
authors.forename: Kenji
authors.initials: K
authors.lastname: Miki
authors.forename: Emiko
authors.initials: E
authors.lastname: Ito
authors.forename: Nagako
authors.initials: N
authors.lastname: Sougawa
authors.forename: Takuji
authors.initials: T
authors.lastname: Kawamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Daimon
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Shimizu
authors.forename: Teruo
authors.initials: T
authors.lastname: Okano
authors.forename: Koichi
authors.initials: K
authors.lastname: Toda
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000502:physiology*; D005260:Female; D006321:Heart / Q000502:physiology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology / Q000637:transplantation*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D032383:Myocytes, Cardiac / Q000502:physiology / Q000637:transplantation*; D011897:Random Allocation; D013524:Surgical Flaps / Q000502:physiology*; D013552:Swine; D013556:Swine, Miniature; D015854:Up-Regulation / Q000502:physiology*
keywords: cell transplantation; induced pluripotent stem cells; regeneration