Pluripotent stem cell-derived mesenchymal stromal cells improve cardiac function and vascularity after myocardial infarction |
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| Institution: | 1. Centre for Heart Research, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia;2. Department of Cardiology, Westmead Hospital, Sydney, Australia;3. Sydney Medical School, University of Sydney, Sydney, Australia;4. Australian Nuclear Science and Technology Organisation, Sydney, Australia;5. School of Chemistry, School of Materials Science and Engineering, Australian Centre for NanoMedicine, University of New South Wales, Sydney, Australia;6. Cynata Therapeutics Limited, Melbourne, Australia;1. Department of Medicine – HeartOtago, Dunedin School of Medicine, University of Otago, New Zealand;2. Department of Cardiology, Southern District Health Board, New Zealand;3. Department of Physiology – HeartOtago, School of Biomedical Sciences, University of Otago, New Zealand;4. Department of Cardiothoracic Surgery, Southern District Health Board, New Zealand;1. Department of Cardiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, China;2. Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin 150001, China;3. Department of Chest Surgery, Affiliated Cancer Hospital and Institution of Guangzhou Medical University, Guangzhou 510095, China;4. Department of Ultrasonography, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, China;5. Department of Cardiovascular surgery, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, China;1. Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran;2. Department of Genetics, School of Biological Sciences, Tarbiat Modares University, Tehran, Iran;3. Rajaie Cardiovascular Medical and Research Centre, Iran University of Medical Sciences, Tehran, Iran;4. Echocardiography Research Center, Department of Cardiovascular Medicine, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran;5. Tasnim Biotechnology Research Center (TBRC), Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran;6. Cell and Immunotherapy Department, Breast Cancer Research Center, Motamed Cancer Institute ACECR, Tehran, Iran;7. Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran;8. Department of Surgery and Radiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran;9. Cardiac Primary Prevention Research Center, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran;1. Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China;2. Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China;1. Center of Cardiology, Navy General Hospital, Beijing, China;2. Stem Cell Institute, Academy of Military Medical Sciences, Beijing, China;3. Center of Cardiology, Beijing Tongren Hospital, Beijing, China;4. Department of Cardiology, Armed Police General Hospital, Beijing, China;5. Center of Cardiology, Beijing Chaoyang Hospital, Beijing, China;6. Department of Diagnostic Radiology, Navy General Hospital, Beijing, China;7. Department of Hematology, Navy General Hospital, Beijing, China;8. Department of Ultrasonic Diagnosis, Navy General Hospital, Beijing, China |
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| Abstract: | Background aimsMesenchymal stromal cells (MSCs) have been shown to improve cardiac function after injury and are the subject of ongoing clinical trials. In this study, the authors tested the cardiac regenerative potential of an induced pluripotent stem cell-derived MSC (iPSC-MSC) population (Cymerus MSCs) in a rat model of myocardial ischemia-reperfusion (I/R). Furthermore, the authors compared this efficacy with bone marrow-derived MSCs (BM-MSCs), which are the predominant cell type in clinical trials.MethodsFour days after myocardial I/R injury, rats were randomly assigned to (i) a Cymerus MSC group (n = 15), (ii) a BM-MSC group (n = 15) or (iii) a vehicle control group (n = 14). For cell-treated animals, a total of 5 × 106 cells were injected at three sites within the infarcted left ventricular (LV) wall.ResultsOne month after cell transplantation, Cymerus MSCs improved LV function (assessed by echocardiography) compared with vehicle and BM-MSCs. Interestingly, Cymerus MSCs enhanced angiogenesis without sustained engraftment or significant impact on infarct scar size. Suggesting safety, Cymerus MSCs had no effect on inducible tachycardia or the ventricular scar heterogeneity that provides a substrate for cardiac re-entrant circuits.ConclusionsThe authors here demonstrate that intra-myocardial administration of iPSC-MSCs (Cymerus MSCs) provide better therapeutic effects compared with conventional BM-MSCs in a rodent model of myocardial I/R. Because of its manufacturing scalability, iPSC-MSC therapy offers an exciting opportunity for an “off-the-shelf” stem cell therapy for cardiac repair. |
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