Generation of functional endothelial-like cells from adult mouse germline-derived pluripotent stem cells

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• 作者：Julee Kim ; Sarah Eligehausen ; Martin Stehling ; Sigrid Nikol ; Kinarm Ko ; Johannes Waltenberger ; Rainer Klocke
• 关键词：Germline-derived pluripotent stem cells ; Endothelial cells ; Ischemia ; Cell-based therapy ; Arteriogenesis ; Angiogenesis
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：10 January, 2014
• 年：2014
• 卷：443
• 期：2
• 页码：700-705
• 全文大小：1304 K

文摘

Functional endothelial cells and their progenitors are required for vascular development, adequate vascular function, vascular repair and for cell-based therapies of ischemic diseases. Currently, cell therapy is limited by the low abundance of patient-derived cells and by the functional impairment of autologous endothelial progenitor cells (EPCs). In the present study, murine germline-derived pluripotent stem (gPS) cells were evaluated as a potential source for functional endothelial-like cells.

Cells displaying an endothelial cell-like morphology were obtained from gPS cell-derived embryoid bodies using a combination of fluorescence-activated cell sorting (FACS)-based selection of CD31-positive cells and their subsequent cultivation on OP9 stromal cells in the presence of VEGF-A. Real-time reverse transcriptase polymerase chain reaction, FACS analysis and immunofluorescence staining showed that the gPS cell-derived endothelial-like cells (gPS-ECs) expressed endothelial cell-specific markers including von Willebrand Factor, Tie2, VEGFR2/Flk1, intercellular adhesion molecule 2 and vascular endothelial-cadherin. The high expression of ephrin B2, as compared to Eph B4 and VEGFR3, suggests an arterial rather than a venous or lymphatic differentiation. Their capability to take up Dil-conjugated acetylated low-density lipoprotein and to form capillary-like networks on matrigel confirmed their functionality.

We conclude that gPS cells could be a novel source of endothelial cells potentially suitable for regenerative cell-based therapies for ischemic diseases.