title: Assessment of functional competence of endothelial cells from human pluripotent stem cells in zebrafish embryos.
abstract: Human pluripotent stem cells (hPSCs) are proving to be a valuable source of endothelial cells (ECs), pericytes, and vascular smooth muscle cells (vSMCs). Although an increasing number of phenotypic markers are becoming available to determine the phenotypes of these cells in vitro, the ability to integrate and form functional vessels in the host organism, typically mouse, remains critical for the assessment of EC functional competence. However, current mouse models require relatively large numbers of cells that might be difficult to derive simultaneously from multiple hPSCs lines. Therefore, there is an urgent need for new functional assays that are robust and can be performed with small numbers of cells. Here we describe a novel zebrafish xenograft model to test functionality of hPSC-derived ECs. The assay can be performed in 10 days and requires only ~100-400 human cells per embryo. Thus, the zebrafish xenograft model can be useful for the accurate and rapid assessment of functionality of hPSC-derived ECs in a lower vertebrate model that is widely viewed by regulatory authorities as a more acceptable alternative to adult mice.
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden Einthovenweg 20, 2333, ZC, Leiden, The Netherlands.
authors.forename: Valeria V
authors.initials: VV
authors.lastname: Orlova
authors.forename: Yvette
authors.initials: Y
authors.lastname: Drabsch
authors.forename: Peter
authors.initials: P
authors.lastname: ten Dijke
authors.forename: Christine L
authors.initials: CL
authors.lastname: Mummery
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D004625:Embryo, Nonmammalian / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology*; D064593:Heterografts; D006801:Humans; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000637:transplantation*; D015027:Zebrafish