title: Generation of functional endothelial cells with progenitor-like features from murine induced pluripotent stem cells.
abstract: Induced pluripotent stem cells (iPSCs) have shown great potential in regenerative medicine and research applications like disease modeling or drug discovery. Endothelium is indispensable for vascular homeostasis, whereas endothelial dysfunction could lead to different diseases. Therefore, generating autologous cells, able to restore the endothelial lining, can be crucial for slowing or reversing certain pathological processes. In the current study we show efficient differentiation of murine iPSCs into endothelial cells (ECs) with stable CD34+/Tie-2+/Sca-1+/CD45- phenotype and proven functionality. iPS-derived ECs (iPS-ECs) were positive for phospho-eNOS and von Willebrand factor, and responded to shear stress with up-regulation of KLF-2, KDR, HO-1, and increased nitric oxide and VEGF production. These cells reacted to cytokine stimulation through increase in VCAM-1 and inflammatory cytokine secretion. iPS-ECs showed also certain progenitor features, like expression of progenitor markers (CD34, Sca-1, c-kit) and high clonogenic potential. The angiogenic capacity of iPS-ECs in spheroid sprouting assay was similar to primary ECs, whereas on Matrigel, tube structures could be formed only in the presence of other support cells. Angiogenic potential of iPS-ECs in vivo, was similar to murine endothelial cell line MS-1. Summarizing, our approach enabled generation of functional progenitor-like ECs, which can be used as a research model.
authors: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors: Neli
authors: N
authors: Kachamakova-Trojanowska
authors: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors: Witold
authors: W
authors: Nowak
authors: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors: Krzysztof
authors: K
authors: Szade
authors: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors: Jacek
authors: J
authors: Stepniewski
authors: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland; Department of Clinical Immunology and Transplantology, Collegium Medicum, Jagiellonian University, Krakow, Poland.
authors: Karolina
authors: K
authors: Bukowska-Strakova
authors: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors: Monika
authors: M
authors: Zukowska
authors: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors: Hevidar
authors: H
authors: Taha
authors: Jagiellonian Centre for Experimental Therapeutics, Jagiellonian University, Krakow, Poland.
authors: Antonina
authors: A
authors: Chmura-Skirlinska
authors: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors: Michael
authors: M
authors: Beilharz
authors: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland; Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland. Electronic address: jozef.dulak@uj.edu.pl.
authors: Jozef
authors: J
authors: Dulak
authors: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland. Electronic address: alicja.jozkowicz@uj.edu.pl.
authors: Alicja
authors: A
authors: Jozkowicz
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016513:Mice, SCID; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D016207:Cytokines; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide
keywords: Angiogenesis; Endothelial cells; Induced pluripotent stem cells; Mesenchymal stromal cells; Shear stress