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Abstract 15112: Microfluidic Single Cell Analysis Shows Porcine Induced Pluripotent Stem Cell-Derived Endothelial Cells Improve Myocardial Function by Paracrine Activation
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2012
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Abstract 15112ImmunologyCardiac Progenitor CellsCardiac RegenerationBiomedical EngineeringCardiovascular Translational ResearchRegenerative MedicineAngiogenesisStem CellsAtherosclerosisHealth SciencesParacrine ActivationVascular BiologyPipsc-derived Endothelial CellsStem Cell TherapiesCardiac ReprogrammingCell BiologyInduced Pluripotent Stem CellCardiovascular DiseasePhysiologyStem Cell EngineeringEndothelial DysfunctionPorcine IpscsStem Cell ResearchStem-cell TherapyMedicine
Background: Induced pluripotent stem cells (iPSCs) hold great promise for the development of patient-specific therapies for cardiovascular disease. However, clinical translation will require preclinical optimization and validation of large animal iPSC models. Methods and Results: Porcine adipose stromal cells (pASCs) harvested from 5 Yucatan miniswine were reprogrammed using lentivirus carrying Oct4, Sox2, Klf4, and cMyc at a 4:2:2:1 ratio to generate porcine iPSCs (piPSCs). Immunohistochemistry, quantitative PCR, microarray hybridization, and in vivo angiogenic assays confirmed that piPSC-derived endothelial cells (piPSC-ECs) shared similar morphological and functional properties as endothelial cells isolated from the autologous pig aorta (pAorta-ECs). To demonstrate therapeutic potential of these cells, piPSC-ECs were transplanted into mice with myocardial infarction (n=80). Compared to control, animals transplanted with piPSC-ECs showed significant functional improvement on echocardiography (fractional...