Identification of candidate surface antigens for non-invasive prenatal diagnosis by comparative global gene expression on human fetal mesenchymal stem cells

Gotherstrom, C., Chan, J., O'Donoghue, K. and Fisk, N. M. (2010) Identification of candidate surface antigens for non-invasive prenatal diagnosis by comparative global gene expression on human fetal mesenchymal stem cells. Molecular Human Reproduction, 16 7: 472-480. doi:10.1093/molehr/gaq020


Author Gotherstrom, C.
Chan, J.
O'Donoghue, K.
Fisk, N. M.
Title Identification of candidate surface antigens for non-invasive prenatal diagnosis by comparative global gene expression on human fetal mesenchymal stem cells
Journal name Molecular Human Reproduction   Check publisher's open access policy
ISSN 1360-9947
1460-2407
Publication date 2010-07
Sub-type Article (original research)
DOI 10.1093/molehr/gaq020
Volume 16
Issue 7
Start page 472
End page 480
Total pages 9
Place of publication Oxford, UK
Publisher Oxford University Press
Collection year 2011
Language eng
Formatted abstract
Transplacental passage of circulating first-trimester fetal mesenchymal stem cells (fMSC) raises the prospect of harvesting fetal cells in maternal blood. Despite high sensitivity in model systems, negative selection and culture strategies yield fMSC only rarely in post-termination maternal blood. The different adhesion molecule profile of fMSC to competitor maternal cell types suggests that improved positive selection strategies may facilitate non-invasive prenatal diagnosis. We aimed to identify surface antigens specific to fMSC and not maternal peripheral blood lymphocytes (PBL), using genome-wide analysis of actively expressed transcripts. Maternal PBL and fMSC cultured from first-trimester blood, liver and bone marrow were assessed for global gene expression by Affymetrix U133Plus2.0 arrays. Data were analysed using Affymetrix GCOS01.2. Transcripts present in all fMSC (n = 9) but absent in all PBL samples (n =3) were selected for further analysis of cell-surface membrane molecules by RT-PCR and immunocytochemistry. Of 1544 genes expressed in fMSC and not maternal PBL, filtering for cell-surface molecules yielded 159 genes. Of these, 29 had a mean expression ratio of <300 (P > 0.001), which represented 18 unique genes, and their positive expression in all fMSC samples was confirmed by RT-PCR. Candidates for non-invasive prenatal diagnosis were chosen for further analysis by immunocytochemistry. Surface expression of OSMR and COL1 proteins on all fMSC, but no maternal PBL was confirmed. Identification of novel surface antigens on circulating human fMSC and not maternal PBL facilitates positive selection strategies for isolating fMSC for non-invasive prenatal diagnosis.
© The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org.
Keyword Aneuploidy
Fetal stem cells
Feto-maternal trafficking
Maternal blood
Mesenchymal stromal cells
Hematopoietic Progenitor Cells
Adult Bone-marrow
Maternal blood
Peripheral-blood
Human Placenta
Umbilical-cord
Dna
Differentiation
Amniocentesis
Pregnancy
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes * Received November 25, 2009. * Revision received February 5, 2010. * Accepted March 1, 2010.

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2011 Collection
 
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Created: Sun, 15 Aug 2010, 00:02:38 EST