title: Cell-sheet therapy with omentopexy promotes arteriogenesis and improves coronary circulation physiology in failing heart.
abstract: Cell-sheet transplantation induces angiogenesis for chronic myocardial infarction (MI), though insufﬁcient capillary maturation and paucity of arteriogenesis may limit its therapeutic effects. Omentum has been used clinically to promote revascularization and healing of ischemic tissues. We hypothesized that cell-sheet transplantation covered with an omentum-flap would effectively establish mature blood vessels and improve coronary microcirculation physiology, enhancing the therapeutic effects of cell-sheet therapy. Rats were divided into four groups after coronary ligation; skeletal myoblast cell-sheet plus omentum-flap (combined), cell-sheet only, omentum-flap only, and sham operation. At 4 weeks after the treatment, the combined group showed attenuated cardiac hypertrophy and fibrosis, and a greater amount of functionally (CD31(+)/lectin(+)) and structurally (CD31(+)/α-SMA(+)) mature blood vessels, along with myocardial upregulation of relevant genes. Synchrotron-based microangiography revealed that the combined procedure increased vascularization in resistance arterial vessels with better dilatory responses to endothelium-dependent agents. Serial (13)N-ammonia PET showed better global coronary flow reserve in the combined group, mainly attributed to improvement in the basal left ventricle. Consequently, the combined group had sustained improvements in cardiac function parameters and better functional capacity. Cell-sheet transplantation with an omentum-flap better promoted arteriogenesis and improved coronary microcirculation physiology in ischemic myocardium, leading to potent functional recovery in the failing heart.
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kainuma
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyagawa
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Satsuki
authors.initials: S
authors.lastname: Fukushima
authors.affiliation: Monash Biomedical Imaging Facility and Department of Physiology, Monash University, Melbourne, Australia.
authors.forename: James
authors.initials: J
authors.lastname: Pearson
authors.affiliation: Monash Biomedical Imaging Facility and Department of Physiology, Monash University, Melbourne, Australia.
authors.forename: Yi Ching
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Saito
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Akima
authors.initials: A
authors.lastname: Harada
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Shiozaki
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Iseoka
authors.affiliation: Department of Molecular Imaging in Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Watabe
authors.affiliation: Department of Molecular Imaging in Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watabe
authors.affiliation: Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Genki
authors.initials: G
authors.lastname: Horitsugi
authors.affiliation: Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Mana
authors.initials: M
authors.lastname: Ishibashi
authors.affiliation: Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Ikeda
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Tsuchimochi
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sonobe
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Fujii
authors.affiliation: Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Hisamichi
authors.initials: H
authors.lastname: Naito
authors.affiliation: Japan Synchrotron Radiation Research Institute, Harima, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Umetani
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Okano
authors.affiliation: Division of Organ Replacement Research, Center for Molecular Medicine, Jichi Medical School, Tochigi, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kobayashi
authors.affiliation: Department of Biostatistics, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Daimon
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kuratani
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Toda
authors.affiliation: Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takakura
authors.affiliation: Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hatazawa
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
authors.forename: Mikiyasu
authors.initials: M
authors.lastname: Shirai
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
mesh_terms: D000818:Animals; D002465:Cell Movement; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D003326:Coronary Circulation; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D015870:Gene Expression; D006085:Graft Survival; D006333:Heart Failure / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D006439:Hemodynamics; D009203:Myocardial Infarction / Q000150:complications; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic; D009852:Omentum; D051381:Rats; D012039:Regional Blood Flow; D019737:Transplants; D066253:Vascular Remodeling; D016277:Ventricular Function, Left