Masashi Kawamura1, Shigeru Miyagawa1, Satsuki Fukushima1, Atsuhiro Saito2, Koichi Toda1, Takashi Daimon3, Tatsuya Shimizu4, Teruo Okano4, Yoshiki Sawa1. 1. 1 Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine , Suita, Japan . 2. 2 Medical Center for Translational Research, Osaka University Hospital , Osaka, Japan . 3. 3 Department of Biostatistics, Hyogo College of Medicine , Nishinomiya, Japan . 4. 4 Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University , Tokyo, Japan .
Abstract
INTRODUCTION: Bone marrow-derived autologous human mesenchymal stem cells (MSCs) are one of the most promising cell sources for cell therapy to treat heart failure. The cell sheet technique has allowed transplantation of a large number of cells and enhanced the efficacy of cell therapy. We hypothesized that the transplantation of MSC sheets may be a feasible, safe, and effective treatment for ischemic cardiomyopathy (ICM). METHODS AND RESULTS: Human MSCs acquired from bone marrow were positive for CD73, CD90, and CD105 and negative for CD11b and CD45 by flow cytometry. Ten MSC sheets were created from a total cell number of 1×10(8) MSCs using temperature-responsive culture dishes. These were successfully transplanted over the infarct myocardium of porcine ICM models induced by placing an ameroid constrictor on the left anterior descending coronary artery without any procedural-related complications (MSC group=6: sheet transplantation; sham group=6, oral intake of tacrolimus in both groups). Premature ventricular contractions were rarely detected by Holter electrocardiogram (ECG) in the MSC group in the first week after transplantation. On echocardiography, the cardiac performance of the MSC group was significantly better than that of the sham group at 8 weeks after transplantation. On histological examination 8 weeks after transplantation, left ventricular (LV) remodeling was significantly attenuated compared with the sham group (cardiomyocyte size and interstitial fibrosis were measured). Immunohistochemistry of the von Willebrand factor showed that the vascular density in the infarct border area was significantly greater in the MSC group than the sham group. Expression of angiogenesis-related factors in the infarct border area of the MSC group was significantly greater than that of the sham group, as measured by real-time polymerase chain reaction. CONCLUSIONS: Bone marrow-derived MSC sheets improved cardiac function and attenuated LV remodeling in ICM without major complications, indicating that this strategy would be applicable in clinical settings.
INTRODUCTION: Bone marrow-derived autologous human mesenchymal stem cells (MSCs) are one of the most promising cell sources for cell therapy to treat heart failure. The cell sheet technique has allowed transplantation of a large number of cells and enhanced the efficacy of cell therapy. We hypothesized that the transplantation of MSC sheets may be a feasible, safe, and effective treatment for ischemic cardiomyopathy (ICM). METHODS AND RESULTS:Human MSCs acquired from bone marrow were positive for CD73, CD90, and CD105 and negative for CD11b and CD45 by flow cytometry. Ten MSC sheets were created from a total cell number of 1×10(8) MSCs using temperature-responsive culture dishes. These were successfully transplanted over the infarct myocardium of porcine ICM models induced by placing an ameroid constrictor on the left anterior descending coronary artery without any procedural-related complications (MSC group=6: sheet transplantation; sham group=6, oral intake of tacrolimus in both groups). Premature ventricular contractions were rarely detected by Holter electrocardiogram (ECG) in the MSC group in the first week after transplantation. On echocardiography, the cardiac performance of the MSC group was significantly better than that of the sham group at 8 weeks after transplantation. On histological examination 8 weeks after transplantation, left ventricular (LV) remodeling was significantly attenuated compared with the sham group (cardiomyocyte size and interstitial fibrosis were measured). Immunohistochemistry of the von Willebrand factor showed that the vascular density in the infarct border area was significantly greater in the MSC group than the sham group. Expression of angiogenesis-related factors in the infarct border area of the MSC group was significantly greater than that of the sham group, as measured by real-time polymerase chain reaction. CONCLUSIONS: Bone marrow-derived MSC sheets improved cardiac function and attenuated LV remodeling in ICM without major complications, indicating that this strategy would be applicable in clinical settings.
Authors: Konstantinos E Hatzistergos; Henry Quevedo; Behzad N Oskouei; Qinghua Hu; Gary S Feigenbaum; Irene S Margitich; Ramesh Mazhari; Andrew J Boyle; Juan P Zambrano; Jose E Rodriguez; Raul Dulce; Pradip M Pattany; David Valdes; Concepcion Revilla; Alan W Heldman; Ian McNiece; Joshua M Hare Journal: Circ Res Date: 2010-07-29 Impact factor: 17.367
Authors: Nicola Smart; Catherine A Risebro; Athalie A D Melville; Kelvin Moses; Robert J Schwartz; Kenneth R Chien; Paul R Riley Journal: Nature Date: 2006-11-15 Impact factor: 49.962
Authors: John W MacArthur; Andrew B Goldstone; Jeffrey E Cohen; William Hiesinger; Y Joseph Woo Journal: Eur J Cardiothorac Surg Date: 2016-09 Impact factor: 4.191
Authors: A Cagdas Yorukoglu; A Esat Kiter; Semih Akkaya; N Lale Satiroglu-Tufan; A Cevik Tufan Journal: Stem Cells Int Date: 2017-11-05 Impact factor: 5.443