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Hum. Reprod. Advance Access originally published online on January 31, 2008
Human Reproduction 2008 23(4):928-933; doi:10.1093/humrep/dem417
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© The Author 2008. 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

High frequency of fetal cells within a primitive stem cell population in maternal blood

Magued A. Mikhail1, Hanane M’Hamdi1, Jonathan Welsh2, Natasa Levicar1, Stephen B. Marley2, Joanna P. Nicholls1, Nagy A. Habib1, Louay S. Louis3, Nicholas M. Fisk3 and Myrtle Y. Gordon2,4

1 Department of Surgery, Imperial College London, Faculty of Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, UK 2 Department of Haematology, Imperial College London, Faculty of Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, UK 3 Department of Reproductive Biology, Imperial College London, Faculty of Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, UK

4 Correspondence address. Tel: +44-208-383-3430; E-mail: myrtle.gordon{at}imperial.ac.uk

BACKGROUND: During pregnancy, fetal cells enter the maternal bloodstream resulting in fetal cell microchimerism. The fetal cells persist in the mother for decades and colonize a variety of maternal organs. They are associated with maternal autoimmune diseases and may also participate in tissue repair. The identity of the microchimeric cells is not certain but they must be able to persist long-term and have potential for multitissue differentiation.

METHODS AND RESULTS: Here we tested the hypothesis that the fetal microchimeric cells are primitive stem cells, represented by CD34+ adherent cells, which have a wide potential for differentiation. We isolated these stem cells from the blood of pregnant females (n = 25) and detected fetal cells of the correct gender, using fluorescence in situ hybridization, in a high proportion (71% male fetuses and 90% female fetuses; false positive rate 11%, false negative rate 29%) of cases. By RT–PCR, we demonstrated that the cells express Oct-4, Nanog and Rex-1. No fetal cells were detected in the mononuclear or total CD34+ cell populations but high frequencies (mean 11.8%) of fetal cells were detected in the adherent CD34+ cell population.

CONCLUSIONS: These results identify adherent CD34+ stem cells as candidate fetal microchimeric cells, which are capable of sustaining the fetal cell population in the long term and have the ability to colonize multiple tissues and organs.

Key words: microchimerism/fetal stem cells/CD34

Submitted on July 18, 2007; resubmitted on October 31, 2007; accepted on November 14, 2007.


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