Improving survival and efficacy of pluripotent stem cell–derived cardiac grafts |
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Authors: | Creighton W Don Charles E Murry |
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Institution: | 1. Department of Medicine/Cardiology, University of Washington, , Seattle, WA, USA;2. Departments of Pathology and Bioengineering, Center for Cardiovascular Biology, Institute for Stem Cell and Regenerative Medicine, University of Washington, , Seattle, WA, USA |
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Abstract: | Human embryonic stem cells (hESCs) can be differentiated into structurally and electrically functional myocardial tissue and have the potential to regenerate large regions of infarcted myocardium. One of the key challenges that needs to be addressed towards full‐scale clinical application of hESCs is enhancing survival of the transplanted cells within ischaemic or scarred, avascular host tissue. Shortly after transplantation, most hESCs are lost as a result of multiple mechanical, cellular and host factors, and a large proportion of the remaining cells undergo apoptosis or necrosis shortly thereafter, as a result of loss of adhesion‐related signals, ischaemia, inflammation or immunological rejection. Blocking the apoptotic signalling pathways of the cells, using pro‐survival cocktails, conditioning hESCs prior to transplant, promoting angiogenesis, immunosuppressing the host and using of bioengineered matrices are among the emerging techniques that have been shown to optimize cell survival. This review presents an overview of the current strategies for optimizing cell and host tissue to improve the survival and efficacy of cardiac cells derived from pluripotent stem cells. |
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Keywords: | cardiac cardiomyocyte myocardium pluripotent stem cell human embryonic stem cell differentiation apoptosis homing tissue engineering hydrogel |
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