Identification of fetal mesenchymal stem cells in maternal blood: Implications for non-invasive prenatal diagnosis

O’Donoghue, K., Choolani, M., Chan, J., de la Fuente, J., Kumar, S., Campagnoli, C., Bennett, P. R., Roberts, I. A. G. and Fisk, N. M. (2003) Identification of fetal mesenchymal stem cells in maternal blood: Implications for non-invasive prenatal diagnosis. Molecular Human Reproduction, 9 8: 497-502. doi:10.1093/molehr/gag063


Author O’Donoghue, K.
Choolani, M.
Chan, J.
de la Fuente, J.
Kumar, S.
Campagnoli, C.
Bennett, P. R.
Roberts, I. A. G.
Fisk, N. M.
Title Identification of fetal mesenchymal stem cells in maternal blood: Implications for non-invasive prenatal diagnosis
Journal name Molecular Human Reproduction   Check publisher's open access policy
ISSN 1360-9947
1460-2407
Publication date 2003-08-01
Year available 2003
Sub-type Article (original research)
DOI 10.1093/molehr/gag063
Open Access Status
Volume 9
Issue 8
Start page 497
End page 502
Total pages 6
Place of publication Oxford, U.K.
Publisher Published for the European Society for Human Reproduction and Embryology by Oxford University Press
Language eng
Subject 111401 Foetal Development and Medicine
111402 Obstetrics and Gynaecology
1114 Paediatrics and Reproductive Medicine
Abstract Strategies for genetic prenatal diagnosis on fetal cells in the maternal circulation have been limited by lack of a cell type present only in fetal blood. However, the recent identification of mesenchymal stem cells (MSC) in first trimester fetal blood offers the prospect of targeting MSC for non-invasive prenatal diagnosis. We developed protocols for fetal MSC enrichment from maternal blood and determined sensitivity and specificity in mixing experiments of male fetal MSC added to female blood, in dilutions from 1 in 10(5) to 10(8). We then used the optimal protocol to isolate fetal MSC from maternal blood in the first trimester, using blood taken after surgical termination of pregnancy as a model of increased feto-maternal haemorrhage. In model mixtures, we could amplify one male fetal MSC in 2.5x10(7) adult female nucleated cells, yielding a 100% pure population of fetal cells, but not one fetal MSC in 10(8) nucleated cells. Fetal MSC were identified in one of 20 post-termination maternal blood samples and confirmed as fetal MSC by XY fluorescence in-situ hybridization (FISH), immunophenotyping and osteogenic and adipogenic differentiation. We report the isolation of fetal MSC from maternal blood; however, their rarity in post-termination blood suggests they are unlikely to have a role in non-invasive prenatal diagnosis. Failure to locate these cells routinely may be attributed to their low frequency in maternal blood, to sensitivity limitations of enrichment technology, and/or to their engraftment in maternal tissues soon after transplacental passage. We speculate that gender microchimerism in post-reproductive maternal tissues might result from feto-maternal trafficking of MSC in early pregnancy.
Formatted abstract
Strategies for genetic prenatal diagnosis on fetal cells in the maternal circulation have been limited by lack of a cell type present only in fetal blood. However, the recent identification of mesenchymal stem cells (MSC) in first trimester fetal blood offers the prospect of targeting MSC for non-invasive prenatal diagnosis. We developed protocols for fetal MSC enrichment from maternal blood and determined sensitivity and specificity in mixing experiments of male fetal MSC added to female blood, in dilutions from 1 in 105 to 108. We then used the optimal protocol to isolate fetal MSC from maternal blood in the first trimester, using blood taken after surgical termination of pregnancy as a model of increased feto-maternal haemorrhage. In model mixtures, we could amplify one male fetal MSC in 2.5x107 adult female nucleated cells, yielding a 100% pure population of fetal cells, but not one fetal MSC in 108 nucleated cells. Fetal MSC were identified in one of 20 post-termination maternal blood samples and confirmed as fetal MSC by XY fluorescence in-situ hybridization (FISH), immunophenotyping and osteogenic and adipogenic differentiation. We report the isolation of fetal MSC from maternal blood; however, their rarity in post-termination blood suggests they are unlikely to have a role in non-invasive prenatal diagnosis. Failure to locate these cells routinely may be attributed to their low frequency in maternal blood, to sensitivity limitations of enrichment technology, and/or to their engraftment in maternal tissues soon after transplacental passage. We speculate that gender microchimerism in post-reproductive maternal tissues might result from feto-maternal trafficking of MSC in early pregnancy.
©European Society of Human Reproduction and Embryology 2003; all rights reserved.

Keyword Fetal cells
Maternal blood
Mesenchymal stem cells
Microchimerism
Non-invasive prenatal diagnosis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
 
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Created: Thu, 19 Mar 2009, 01:39:12 EST by Ms Julie Schofield on behalf of Institute for Molecular Bioscience