title: Multilayered adipose-derived regenerative cell sheets created by a novel magnetite tissue engineering method for myocardial infarction.
abstract: BACKGROUND
  Adipose-derived regenerative cells (ADRCs) are a promising source of autologous stem cells for regeneration and repair of damaged tissue. Herein, we investigated the therapeutic potential of ADRC sheets created by a magnetite tissue engineering technology (Mag-TE) for myocardial infarction.
  
  
  RESULTS
  Adipose tissue was obtained from wild-type (WT) mice and ADRCs were isolated. ADRCs incubated with magnetic nanoparticle-containing liposomes (MCLs) were cultured. MCL-labeled ADRCs were mixed with a diluted extracellular matrix (ECM) precursor, and a magnet was placed on the reverse side. Magnetized ADRCs formed multilayered cell sheets after a 24-h incubation. WT mice were subjected to myocardial infarction by permanent ligation of the left anterior descending artery. We then transplanted the constructed ADRC sheet or a cell-free collagen gel sheet, as a control, onto the infarcted myocardium using an Alnico magnet before skin closure. Cardiac parameters were measured by echocardiogram, and angiogenesis was determined by tissue capillary density. ADRC sheet-treated mice showed significant improvements in systolic function, infarct wall thinning, and fibrotic length after myocardial infarction. ADRC sheet implantation also promoted angiogenesis in both the infarct area and the border zone in WT mice after myocardial infarction. The angiogenic effects of ADRC sheets were attributed to an increased expression of VEGF and bFGF mRNA in ischemic hearts.
  
  
  CONCLUSIONS
  ADRC sheets created by this Mag-TE method protect the heart against pathological cardiac remodeling. Our ADRC sheets have the potential to be a novel regenerative strategy for ischemic heart disease.
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ishii
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Japan. Electronic address: rshibata@med.nagoya-u.ac.jp.
authors.forename: Rei
authors.initials: R
authors.lastname: Shibata
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Department of Molecular Cardiology, Nagoya University Graduate School of Medicine, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ouchi
authors.affiliation: Department of Otolaryngology, Aichi Medical University, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Tanigawa
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Japan.
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Kanemura
authors.affiliation: Kyushu University, Department of Chemical Engineering Faculty of Engineering, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ito
authors.affiliation: Department of Biotechnology, Nagoya University Graduate School of Engineering, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Honda
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Japan. Electronic address: murohara@med.nagoya-u.ac.jp.
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000637:transplantation*; D000818:Animals; D002478:Cells, Cultured; D052203:Ferrosoferric Oxide / Q000008:administration & dosage*; D048091:Guided Tissue Regeneration / Q000379:methods*; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D011897:Random Allocation; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D052203:Ferrosoferric Oxide
keywords: Adipose-derived regenerative cells; Magnetic nanoparticle; Myocardial infarction; Stem cell; Tissue engineering