Generation of functional endothelial cells with progenitor-like features from murine induced pluripotent stem cells
| Autor: | Neli Kachamakova-Trojanowska, Karolina Bukowska-Strakova, Antonina Chmura-Skirlinska, Krzysztof Szade, Hevidar Taha, Alicja Jozkowicz, Jacek Stępniewski, Monika Zukowska, Jozef Dulak, Witold Nowak, Michael Beilharz |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Vascular Endothelial Growth Factor A
0301 basic medicine Endothelium induced pluripotent stem cells Physiology Angiogenesis Induced Pluripotent Stem Cells CD34 Mice Nude Neovascularization Physiologic Vascular Cell Adhesion Molecule-1 Mice SCID Biology Nitric Oxide shear stress Cell Line Mice angiogenesis 03 medical and health sciences medicine Animals Humans Induced pluripotent stem cell Pharmacology Matrigel Mesenchymal stem cell Endothelial Cells Cell Differentiation endothelial cells Up-Regulation Cell biology Mice Inbred C57BL Endothelial stem cell 030104 developmental biology medicine.anatomical_structure Immunology Cytokines Molecular Medicine Cytokine secretion mesenchymal stromal cells |
| Zdroj: | Vascular Pharmacology. 86:94-108 |
| ISSN: | 1537-1891 |
| DOI: | 10.1016/j.vph.2016.07.008 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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