Jones, GN;
Moschidou, D;
Puga-Iglesias, TI;
Kuleszewicz, K;
Vanleene, M;
Shefelbine, SJ;
Bou-Gharios, G;
... Guillot, PV; + view all
(2012)
Ontological differences in first compared to third trimester human fetal placental chorionic stem cells.
PLOS One
, 7
(9)
, Article e43395. 10.1371/journal.pone.0043395.
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Abstract
Human mesenchymal stromal/stem cells (MSC) isolated from fetal tissues hold promise for use in tissue engineering applications and cell-based therapies, but their collection is restricted ethically and technically. In contrast, the placenta is a potential source of readily-obtainable stem cells throughout pregnancy. In fetal tissues, early gestational stem cells are known to have advantageous characteristics over neonatal and adult stem cells. Accordingly, we investigated whether early fetal placental chorionic stem cells (e-CSC) were physiologically superior to their late gestation fetal chorionic counterparts (l-CSC). We showed that e-CSC shared a common phenotype with l-CSC, differentiating down the osteogenic, adipogenic and neurogenic pathways, and containing a subset of cells endogenously expressing NANOG, SOX2, c-MYC, and KLF4, as well as an array of genes expressed in pluripotent stem cells and primordial germ cells, including CD24, NANOG, SSEA4, SSEA3, TRA-1-60, TRA-1-81, STELLA, FRAGILIS, NANOS3, DAZL and SSEA1. However, we showed that e-CSC have characteristics of an earlier state of stemness compared to l-CSC, such as smaller size, faster kinetics, uniquely expressing OCT4A variant 1 and showing higher levels of expression of NANOG, SOX2, c-MYC and KLF4 than l-CSC. Furthermore e-CSC, but not l-CSC, formed embryoid bodies containing cells from the three germ layer lineages. Finally, we showed that e-CSC demonstrate higher tissue repair in vivo; when transplanted in the osteogenesis imperfecta mice, e-CSC, but not l-CSC increased bone quality and plasticity; and when applied to a skin wound, e-CSC, but not l-CSC, accelerated healing compared to controls. Our results provide insight into the ontogeny of the stemness phenotype during fetal development and suggest that the more primitive characteristics of early compared to late gestation fetal chorionic stem cells may be translationally advantageous.
| Type: | Article |
|---|---|
| Title: | Ontological differences in first compared to third trimester human fetal placental chorionic stem cells. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0043395 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0043395 |
| Language: | English |
| Additional information: | © Jones et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This research was funded by Genesis Research Trust, Henry Smith Charity and Action Medical Research. GNJ was supported by the Medical Research Council. DM was supported by Kidney Research United Kingdom. KK was supported by Biotechnology and Biological Science Research Council. PDC was supported by Great Ormond Street Hospital Children's Charity. ALD is supported by the National Institute for Health Research (NIHR) through a Senior Lectureship and the Department of Health's NIHR Biomedical Research Centers funding scheme. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| Keywords: | Adult, Animals, Biological Markers, Cell Differentiation, Chorion, Female, Fetal Stem Cells, Humans, Mesenchymal Stromal Cells, Mice, Mice, Transgenic, Placenta, Pluripotent Stem Cells, Pregnancy, Pregnancy Trimester, First, Pregnancy Trimester, Third, Skin, Stage-Specific Embryonic Antigens, Stem Cell Transplantation, Time Factors, Transplantation, Heterologous, Wound Healing |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Maternal and Fetal Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1375403 |
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