Abstract
Parthenogenetic stem cells (PSCs) are a promising candidate donor for cell therapy applications. Similar to embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), PSCs exhibit self-renewing capacity and clonogenic proliferation in vitro. PSCs exhibit largely haploidentical genotype, and as such may constitute an attractive population for allogenic applications. In this study, PSCs isolated from transgenic mice carrying a cardiomyocyte-restricted reporter transgene to permit tracking of donor cells were genetically modified to carry a cardiomyocyte-restricted aminoglycoside phosphotransferase expression cassette (MHC-neor/pGK-hygror) to permit the generation of highly enriched cardiomyocyte cultures from spontaneously differentiating PSCs by simple selection with the neomycin analogue G148. Following engraftment into isogenic recipient hearts, the selected cardiomyocytes formed a functional syncytium with the host myocardium as evidenced by the presence of entrained intracellular calcium transients. These cells thus constitute a potential source of therapeutic donor cells.
Highlights
Acute myocardial infarction commonly results in the loss of large numbers of cardiomyocytes
We have previously shown that highly enriched populations of cardiomyocytes can be readily generated using embryonic stem cells (ESCs) carrying a transgene comprised of the lineage-restricted cardiac myosin heavy chain (MHC) promoter and sequences encoding aminoglycoside phosphotransferase [5]
Parthenogenetic stem cells (PSCs) were electroporated with a ubiquitously-expressed ds-Red reporter transgene, and transfection efficiency was calculated by the percent of ds-Red+ cells vs. the number of attached cells 24 h after electroporation
Summary
Acute myocardial infarction commonly results in the loss of large numbers of cardiomyocytes. Considerable effort has been invested in developing strategies to repair myocardial damage, including the direct injection of donor cardiomyocytes [1,2] as well as the generation and implantation of bioengineered patches, including two dimensional sheets of cells [3] as well as three dimensional constructs [4]. Initial proof of concept studies utilized fetal cardiomyocytes [1], which were followed shortly by embryonic stem cell (ESC)-derived cardiomyocytes [5]. Donor human ESC-derived cardiomyocytes were shown to functionally engraft monkey hearts with small experimentally induced infarcts. PLOS ONE | DOI:10.1371/journal.pone.0131511 June 25, 2015
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