Functional characterization and expression profiling of human induced pluripotent stem cell- and embryonic stem cell-derived endothelial cells.

Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, California 94305-5344, USA.
Stem cells and development (Impact Factor: 4.15). 10/2011; 20(10):1701-10. DOI: 10.1089/scd.2010.0426
Source: PubMed

ABSTRACT With regard to human induced pluripotent stem cells (hiPSCs), in which adult cells are reprogrammed into embryonic-like cells using defined factors, their functional and transcriptional expression pattern during endothelial differentiation has yet to be characterized. In this study, hiPSCs and human embryonic stem cells (hESCs) were differentiated using the embryoid body method, and CD31(+) cells were sorted. Fluorescence activated cell sorting analysis of hiPSC-derived endothelial cells (hiPSC-ECs) and hESC-derived endothelial cells (hESC-ECs) demonstrated similar endothelial gene expression patterns. We showed functional vascular formation by hiPSC-ECs in a mouse Matrigel plug model. We compared the gene profiles of hiPSCs, hESCs, hiPSC-ECs, hESC-ECs, and human umbilical vein endothelial cells (HUVECs) using whole genome microarray. Our analysis demonstrates that gene expression variation of hiPSC-ECs and hESC-ECs contributes significantly to biological differences between hiPSC-ECs and hESC-ECs as well as to the "distances" among hiPSCs, hESCs, hiPSC-ECs, hESC-ECs, and HUVECs. We further conclude that hiPSCs can differentiate into functional endothelial cells, but with limited expansion potential compared with hESC-ECs; thus, extensive studies should be performed to explore the cause and extent of such differences before clinical application of hiPSC-ECs can begin.

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    The Canadian journal of cardiology 08/2014; · 3.12 Impact Factor
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    ABSTRACT: Introduction The differentiated cell lineages from human em-bryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) have shown their potential in regenerative medicine. However, the functional and transcriptional microRNA (miRNA) expression pattern during endothelial differentiation has yet to be characterized. Methods In this study, hESCs and hiPSCs were differentiated into endothelial cells (ECs). Then the endothelial-related gene profiling and miRNA profiling of hiPSCs, hESCs, hiPSCs derived endothelial cells (hiPSC-ECs), hESC derived endo-thelial cells (hESC-ECs) and human umbilical vein endothe-lial cells (HUVECs) were compared using RT-PCR Array. The data was analyzed using the data analysis system on QIAGEN's website. Results Our analysis demonstrated that the endothelial differ-entiation was triggered after EB formation and the EC-associated genes were up-regulated swiftly in both hESC-EBs and hiPSC-EBs; hiPSC-ECs and hESC-ECs had the sim-ilar EC-associated gene expression patterns. Moreover, we re-port here the first miRNA profiling study of hiPSC-ECs. An-alyzing 376 unique miRNAs, we have identified several inter-esting miRNAs, including miR-20a, miR-20b, miR-222, miR-210, which have been previously reported to be involved in endothelial differentiation and show surprising expression pat-terns across our samples. We also identified novel miRNAs, such as miR-125a-5p, miR-149, miR-296-5p, miR-100, miR-27b, miR-181a and miR-137, which were up-regulated in both hiPSC-ECs and hESC-ECs during endothelial differentiation. Conclusion hiPSC-ECs and hESC-ECs exhibited a high de-gree of similarity with HUVECs in EC-associated genes ex-pression. And the miRNA profiling analysis revealed signifi-cant differences between hiPSCs and hESCs, but a high de-gree of similarity between hiPSC-ECs and hESC-ECs.
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May 22, 2014