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Repair of infarcted myocardium using mesenchymal stem cell seeded small intestinal submucosa in rabbits
Authors:Mei Yun Tan  Wei Zhi  Ren Qian Wei  Yong Can Huang  Kun Peng Zhou  Bo Tan  Li Deng  Jing Cong Luo  Xiu Qun Li  Hui Qi Xie  Zhi Ming Yang
Institution:1. Urological Diseases Research Center, Boston Children''s Hospital, Boston, MA 02115, USA;2. Department of Surgery, Harvard Medical School, Boston, MA 02115, USA;3. Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA;1. State Key Laboratory of Hydraulics and Mountain River Engineering, College of Water Resources and Hydropower, Sichuan University, Chengdu 610065, Sichuan, China;2. Department of Civil and Environmental Engineering, University of Pittsburgh, Pittsburgh, PA 15261 USA;3. Department of Mechanical Engineering and Material Science, University of Pittsburgh, Pittsburgh, PA 15261 USA;4. Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261 USA;1. Department of Otolaryngology, School of Medicine, Ajou University, Suwon, South Korea;2. Department of Molecular Science & Technology, Ajou University, Suwon, South Korea;1. Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan, People''s Republic of China;2. Laboratory of Stem Cell and Tissue Engineering, West China Hospital, Sichuan University, Sichuan, People''s Republic of China;3. Department of Orthopedics, The People''s No. 3 Hospital of Anyang, Anyang, Henan, People''s Republic of China;1. Division of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute, 256 Grays Inn Road, London WC1X 8LD, UK;2. Applied Biomedical Engineering Group, Division of Medicine, University College London, Gower St, London WC1E 6BT, UK;3. Department of Nanobiomedical Science & BK21 Plus NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea;4. Institute of Tissue Regeneration Engineering & College of Dentistry, Dankook University, Cheonan 330-714, Republic of Korea
Abstract:Myocardial infarction (MI) remains a common and deadly disease. Using tissue-engineered cardiac grafts to repair infarcted myocrdium is considered to be a therapeutic approach. This study tested the feasibility of using MSCs-seeded SIS to repair chronic myocardial infarction in a rabbit model. MI in rabbits was created by ligation of the left anterior descending artery. BrdU-labeled mesenchymal stem cells (MSCs) were seeded on the small intestinal submucosa and cultured for 5–7 days prior to implantation. Four weeks after myocardial infarction, cardiac grafts were implanted onto the epicardial surface of infarcted myocardium. Four weeks after implantation of the membranes, a serial of tests including echocardiography, hemodynamics, histology and immunohistochemistry were undertaken to evaluate the effect of the implanted grafts on recovery of the infarcted myocardium. It was shown that left ventricular contractile function and dimension, the capillary density of the infarcted region, and myocardial pathological changes were significantly improved in rabbits implanted either SIS or MSCs-seeded SIS. But the MSCs-seeded SIS was more effective. Immunofluorescence staining demonstrated the migration of Brdu-labeled MSCs from the membrane into the infarcted area and their differentiation to cardiomyocytes and smooth muscle cells. Taken together, these results suggest that MSCs-seeded SIS can be used to repair chronic myocardial infarction, which enhances myocardial regeneration.
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