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Tim Kamp, Professor, Medicine; & Will Burlingham, Professor, Surgery, “Testing Immunogenicity of Human Pluripotent Stem Cell-derived Cardiac Grafts”
November 13, 2018 @ 12:00 pm - 1:00 pm
Topic: Testing Immunogenicity of Human Pluripotent Stem Cell-derived Cardiac Grafts
Abstract: Heart disease remains a major cause of death and disability in the United States. Following a myocardial infarction, functioning heart muscle is lost and replaced by scar tissue which can ultimately lead to heart failure. Given that the adult human heart lacks an ability to repair or regenerate, strategies to generate new heart tissue using cell therapies are actively being investigated. Human pluripotent stem cells provide a promising cell source to generate human cardiomyocytes that can re-muscularize the damaged heart based on pre-clinical studies in animal models. However, important barriers need to be overcome before the promise of this therapy can be fully realized. One major barrier for use of allogeneic cell products from human pluripotent stem cells is immune rejection of the grafted cells. Sixty years after the first human kidney transplant we know that some components of the allograft are either not at all or weakly immunogenic, while other tissue-resident cells evoke a powerful immune response. An example of the latter is the dendritic cell (DC), the discovery of which earned Ralph M. Steinman a Nobel Prize in 2011. Though few in number these cells are primarily responsible for triggering rejection of organ/tissue transplants, while other cells such endothelial, epithelial and fibroblast cells trigger much weaker immune responses. It stands to reason, therefore that “pure” cardiomyocyte (CM) grafts derived from iPS cells and CM progenitors will evoke an immune response weaker than that toward a heart transplant, for example. We will explore the functional and immunological parameters that make for ideal cardiac “repair” by iPS-derived tissue, as an alternative to heart transplantation. We will also consider the role of exosomes, virus-like particles produced by mesenchymal and hematopoietic cells, in promoting either acute rejection, or instead, active immune tolerance to the graft’s allo-antigens.