Masakazu Ishii1, Rei Shibata2, Yuuki Shimizu1, Takashi Yamamoto1, Kazuhisa Kondo1, Yoko Inoue1, Noriyuki Ouchi3, Tohru Tanigawa4, Noriyoshi Kanemura1, Akira Ito5, Hiroyuki Honda6, Toyoaki Murohara7. 1. Department of Cardiology, Nagoya University Graduate School of Medicine, Japan. 2. Department of Cardiology, Nagoya University Graduate School of Medicine, Japan. Electronic address: rshibata@med.nagoya-u.ac.jp. 3. Department of Molecular Cardiology, Nagoya University Graduate School of Medicine, Japan. 4. Department of Otolaryngology, Aichi Medical University, Japan. 5. Kyushu University, Department of Chemical Engineering Faculty of Engineering, Japan. 6. Department of Biotechnology, Nagoya University Graduate School of Engineering, Japan. 7. Department of Cardiology, Nagoya University Graduate School of Medicine, Japan. Electronic address: murohara@med.nagoya-u.ac.jp.
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. METHODS AND 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.
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. METHODS AND 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: Maribella Domenech; Lilliana Polo-Corrales; Jaime E Ramirez-Vick; Donald O Freytes Journal: Tissue Eng Part B Rev Date: 2016-07-21 Impact factor: 6.389
Authors: Panithi Sukho; Jolle Kirpensteijn; Jan Willem Hesselink; Gerjo J V M van Osch; Femke Verseijden; Yvonne M Bastiaansen-Jenniskens Journal: Stem Cell Rev Rep Date: 2017-04 Impact factor: 5.739