title: Autologous preconditioned mesenchymal stem cell sheets improve left ventricular function in a rabbit old myocardial infarction model.
abstract: Mesenchymal stem cells (MSCs) constitute one of the most powerful tools for therapeutic angiogenesis in infarcted hearts. However, conventional MSC transplantation approaches result in insufficient therapeutic effects due to poor retention of graft cells in severe ischemic diseases. Cell sheet technology has been developed as a new method to prolong graft cell retention even in ischemic tissue. Recently, we demonstrated that hypoxic pretreatment enhances the therapeutic efficacy of cell sheet implantation in infarcted mouse hearts. In this study, we investigated whether hypoxic pretreatment activates the therapeutic functions of bone marrow-derived MSC (BM-MSC) sheets and improves cardiac function in rabbit infarcted hearts following autologous transplantation. Production of vascular endothelial growth factor (VEGF) was increased in BM-MSC monolayer sheets and it peaked at 48 h under hypoxic culture conditions (2% O2). To examine in vivo effects, preconditioned autologous BM-MSC sheets were implanted into a rabbit old myocardial infarction model. Implantation of preconditioned BM-MSC sheets accelerated angiogenesis in the peri-infarcted area and decreased the infarcted area, leading to improvement of the left ventricular function of the infarcted heart. Importantly, the therapeutic efficacy of the preconditioned BM-MSC sheets was higher than that of standardly cultured sheets. Thus, implantation of autologous preconditioned BM-MSC sheets is a feasible approach for enhancing therapeutic angiogenesis in chronically infarcted hearts.
authors.affiliation: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine Ube, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of MedicineUbe, Japan; Department of Medical Education, Yamaguchi University Graduate School of MedicineUbe, Japan.
authors.forename: Bungo
authors.initials: B
authors.lastname: Shirasawa
authors.affiliation: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine Ube, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Takeuchi
authors.affiliation: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine Ube, Japan.
authors.forename: Daichi
authors.initials: D
authors.lastname: Kawamura
authors.affiliation: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine Ube, Japan.
authors.forename: Tamami
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine Ube, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Samura
authors.affiliation: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine Ube, Japan.
authors.forename: Arata
authors.initials: A
authors.lastname: Nishimoto
authors.affiliation: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of MedicineUbe, Japan; Center for Regenerative Medicine, Yamaguchi University Graduate School of MedicineUbe, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ueno
authors.affiliation: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine Ube, Japan.
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Morikage
authors.affiliation: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of MedicineUbe, Japan; Center for Regenerative Medicine, Yamaguchi University Graduate School of MedicineUbe, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Hosoyama
authors.affiliation: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine Ube, Japan.
authors.forename: Kimikazu
authors.initials: K
authors.lastname: Hamano
keywords: Old myocardial infarction; cell sheet; cell-based therapy; hypoxic preconditioning; mesenchymal stem cells