Abstract
ABSTRACTGeneration of human cardiomyocytes from cells derived from various sources, including skin biopsy, has been made possible by breakthrough advances in stem cell research. However, it is attractive to build up a negligibly invasive way to create induced pluripotent stem (iPS) cells. In this study, we created iPS cells from human urine-derived epithelial cells by gene transduction using lentiviral vectors in a totally noninvasive manner. Then, we induced the differentiation of iPS cells into functional cardiomyocytes both in vitro and in vivo. Action potentials were recorded in putative cardiomyocytes and spontaneous beating cells were observed. Our results offered an alternative method to generate cardiomyocytes in a totally noninvasive manner from an easily accessible source. The availability of urine and its potent reprogramming characteristics will provide opportunities for the use of cells with specific genotypes to study the pathogenesis and molecular mechanisms of disease in vitro.
Highlights
Heart failure is usually caused by loss of working myocardium and occupies high prevalence of death and disability (Roger, 2017)
Pluripotency markers In order to test whether our putative human Induced pluripotent stem (iPS) cells express human embryonic stem cell markers, such as Oct4, Nanog, SSEA-4 and TRA-1-60, immunofluorescence staining was performed on welldefined colonies after 10 passages
Positive results were obtained from the staining of Oct4, SSEA-4, Nanog and TRA-1-60 (Fig. S1A), which was in consistent with flow cytometry analysis: Oct4 (99.2±6.0%), SSEA-4 (98.8±6.7%), Nanog (98.6±7.1%) and TRA1-60 (99.6±6.6%) (n=3, Fig. S1B). These results indicated that the reprogrammed human urine-derived epithelial cells express these typical embryonic stem cells (ESCs) markers
Summary
Heart failure is usually caused by loss of working myocardium and occupies high prevalence of death and disability (Roger, 2017). Human iPS cells have been produced from a variety of materials, including skin, embryonic tissue and umbilical cord blood (Yu et al, 2007; Takahashi et al, 2008; Aasen et al, 2008; Giorgetti et al, 2009; Haase et al, 2009; Esteban et al, 2010; Cai et al, 2010). This encourages people to assume that iPS cells can be derived from all cell types, and to find a preferred source for reprogramming.
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