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Similar Population of CD133+ and DDX4+ VSEL-Like Stem Cells Sorted from Human Embryonic Stem Cell, Ovarian, and Ovarian Cancer Ascites Cell Cultures: The Real Embryonic Stem Cells?

1
Reproductive Division, Department of Obstetrics and Gynaecology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
2
Department of Molecular Diagnostics, Institute of Oncology Ljubljana, 1000 Ljubljana, Slovenia
3
Gynecological Division, Department of Obstetrics and Gynecology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
*
Author to whom correspondence should be addressed.
Cells 2019, 8(7), 706; https://doi.org/10.3390/cells8070706
Received: 14 May 2019 / Revised: 7 July 2019 / Accepted: 8 July 2019 / Published: 11 July 2019
(This article belongs to the Special Issue Female Germline Stem Cells)
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Abstract

A population of small stem cells with diameters of up to 5 μm resembling very small embryonic-like stem cells (VSELs) were sorted from human embryonic stem cell (hESC) cultures using magnetic-activated cell sorting (MACS) based on the expression of a stem-cell-related marker prominin-1 (CD133). These VSEL-like stem cells had nuclei that almost filled the whole cell volume and expressed stem-cell-related markers (CD133, SSEA-4) and markers of germinal lineage (DDX4/VASA, PRDM14). They were comparable to similar populations of small stem cells sorted from cell cultures of normal ovaries and were the predominant cells in ascites of recurrent ovarian cancer. The sorted populations of CD133+ VSEL-like stem cells were quiescent in vitro, except for ascites, and were highly activated after exposure to valproic acid and follicle-stimulating hormone (FSH), indicating a new tool to study these cells in vitro. These VSEL-like stem cells spontaneously formed clusters resembling tumour-like structures or grew into larger, oocyte-like cells and were differentiated in vitro into adipogenic, osteogenic and neural lineages after sorting. We propose the population of VSEL-like stem cells from hESC cultures as potential original embryonic stem cells, which are present in the human embryo, persist in adult human ovaries from the embryonic period of life and are involved in cancer manifestation. View Full-Text
Keywords: human; very small embryonic-like stem cells (VSELs); embryonic stem cells; ovary; ovarian cancer ascites; CD133; DDX4; magnetic-activated cell sorting; differentiation human; very small embryonic-like stem cells (VSELs); embryonic stem cells; ovary; ovarian cancer ascites; CD133; DDX4; magnetic-activated cell sorting; differentiation
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Virant-Klun, I.; Skerl, P.; Novakovic, S.; Vrtacnik-Bokal, E.; Smrkolj, S. Similar Population of CD133+ and DDX4+ VSEL-Like Stem Cells Sorted from Human Embryonic Stem Cell, Ovarian, and Ovarian Cancer Ascites Cell Cultures: The Real Embryonic Stem Cells? Cells 2019, 8, 706.

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