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Functional characterization of iPSC-derived arterial- and venous-like endothelial cells

Autores: Rosa, S.; Praca, C. ; Pitrez, P. R.; Gouveia, P. J.; Aranguren López, Xabier; Ricotti, L.; Ferreira, L. S. (Autor de correspondencia)
Título de la revista: SCIENTIFIC REPORTS
ISSN: 2045-2322
Volumen: 9
Páginas: 3826
Fecha de publicación: 2019
The current work reports the functional characterization of human induced pluripotent stem cells (iPSCs)-arterial and venous-like endothelial cells (ECs), derived in chemically defined conditions, either in monoculture or seeded in a scaffold with mechanical properties similar to blood vessels. iPSC-derived arterial- and venous-like endothelial cells were obtained in two steps: differentiation of iPSCs into endothelial precursor cells (CD31(pos)/KDRpos/VE-Cad(med)/EphB2(neg)/COUP-TFneg) followed by their differentiation into arterial and venous-like ECs using a high and low vascular endothelial growth factor (VEGF) concentration. Cells were characterized at gene, protein and functional levels. Functionally, both arterial and venous-like iPSC-derived ECs responded to vasoactive agonists such as thrombin and prostaglandin E2 (PGE(2)), similar to somatic ECs; however, arterial- like iPSC-derived ECs produced higher nitric oxide (NO) and elongation to shear stress than venous-like iPSC-derived ECs. Both cells adhered, proliferated and prevented platelet activation when seeded in poly(caprolactone) scaffolds. Interestingly, both iPSC-derived ECs cultured in monoculture or in a scaffold showed a different inflammatory profile than somatic ECs. Although both somatic and iPSC-derived ECs responded to tumor necrosis factor-alpha (TNF-alpha) by an increase in the expression of intercellular adhesion molecule 1 (ICAM-1), only somatic ECs showed an upregulation in the expression of E-selectin or vascular cell adhesion molecule 1 (VCAM-1).