title: Teratocarcinomas Arising from Allogeneic Induced Pluripotent Stem Cell-Derived Cardiac Tissue Constructs Provoked Host Immune Rejection in Mice.
abstract: Transplantation of induced pluripotent stem cell-derived cardiac tissue constructs is a promising regenerative treatment for cardiac failure: however, its tumourigenic potential is concerning. We hypothesised that the tumourigenic potential may be eliminated by the host immune response after allogeneic cell transplantation. Scaffold-free iPSC-derived cardaic tissue sheets of C57BL/6 mouse origin were transplanted into the cardiac surface of syngeneic C57BL/6 mice and allogeneic BALB/c mice with or without tacrolimus injection. Syngeneic mice and tacrolimus-injected immunosuppressed allogeneic mice formed teratocarcinomas with identical phenotypes, characteristic, and time courses, as assessed by imaging tools including (18)F-fluorodeoxyglucose-positron emission tomography. In contrast, temporarily immunosuppressed allogeneic mice, following cessation of tacrolimus injection displayed diminished progression of the teratocarcinoma, accompanied by an accumulation of CD4/CD8-positive T cells, and finally achieved complete elimination of the teratocarcinoma. Our results indicated that malignant teratocarcinomas arising from induced pluripotent stem cell-derived cardiac tissue constructs provoked T cell-related host immune rejection to arrest tumour growth in murine allogeneic transplantation models.
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Kawamura
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyagawa
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Satsuki
authors.initials: S
authors.lastname: Fukushima
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Kawamura
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kashiyama
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Ito
authors.affiliation: Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Watabe
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Masuda
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Toda
authors.affiliation: Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.|Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hatazawa
authors.affiliation: Department of Diagnostic Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Morii
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
mesh_terms: D000818:Animals; D001706:Biopsy; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D019788:Fluorodeoxyglucose F18; D023061:Gene Order; D005822:Genetic Vectors / Q000235:genetics; D006084:Graft Rejection / Q000276:immunology*; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D032383:Myocytes, Cardiac / Q000166:cytology / Q000473:pathology*; D049268:Positron-Emission Tomography; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D016559:Tacrolimus / Q000008:administration & dosage; D018243:Teratocarcinoma / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology*; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D019788:Fluorodeoxyglucose F18; D016559:Tacrolimus