Molecular Human Reproduction, Vol. 9, No. 8, 497-502,
August 2003
© 2003 European Society of Human Reproduction and Embryology
Article |
Identification of fetal mesenchymal stem cells in maternal blood: implications for non-invasive prenatal diagnosis
Submitted on April 13, 2003; accepted on May 8, 2003
1 Institute of Reproductive and Developmental Biology, Division of Paediatrics, Obstetrics and Gynaecology and 2 Department of Haematology, Division of Investigative Sciences, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK
3 To whom correspondence should be addressed. e-mail: k.odonoghue{at}imperial.ac.uk
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.
Key words: fetal cells/maternal blood/mesenchymal stem cells/microchimerism/non-invasive prenatal diagnosis
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