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Fetal Microchimerism in the Maternal Mouse Brain: A Novel Population of Fetal Progenitor or Stem Cells Able to Cross the Blood–Brain Barrier?

^a Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore;
^b Department of Clinical Research, Singapore General Hospital, Singapore;
^c National Drug Screening Laboratory, Chinese Pharmaceutical University, Nanjing, China;
^d Genome Information Research Center, Osaka University, Osaka, Japan;
^e Institute of Molecular and Cell Biology, Singapore

Key Words. Fetomaternal microchimerism • Maternal brain • Fetal • Neural differentiation • Neural stem cell • Neural progenitor cell • Pregnancy

Correspondence: Gavin S. Dawe, Ph.D., Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, MD2, 18 Medical Drive, Singapore 117597. Telephone: 65-6516-8874; Fax: 65-6873-7690; e-mail: gavindawe{at}nus.edu.sg; and Zhi-Cheng Xiao, M.D., Ph.D., Department of Clinical Research, Singapore General Hospital, Singapore 169608. Telephone: 65-6326-6195; Fax: 65-6321-3606; e-mail: gcrxzc{at}sgh.com.sg

We investigated whether fetal cells can enter the maternal brain during pregnancy. Female wild-type C57BL/6 mice were crossed with transgenic Green Mice ubiquitously expressing enhanced green fluorescent protein (EGFP). Green Mouse fetal cells were found in the maternal brain. Quantitative real-time polymerase chain reaction (PCR) of genomic DNA for the EGFP gene showed that more fetal cells were present in the maternal brain 4 weeks postpartum than on the day of parturition. After an excitotoxic lesion to the brain, more fetal cells were detected in the injured region. The presence of fetal cells in the maternal brain was also confirmed by quantitative real-time PCR for the sex-determining region of the Y chromosome. Four weeks postpartum, EGFP-positive Green Mouse fetal cells in the maternal brain were found to adopt locations, morphologies, and expression of immunocytochemical markers indicative of perivascular macrophage-, neuron-, astrocyte-, and oligodendrocyte-like cell types. Expression of morphological and immunocytochemical characteristics of neuron- and astrocyte-like cell types was confirmed on identification of fetal cells in maternal brain by Y chromosome fluorescence in situ hybridization. Although further studies are required to determine whether such engraftment of the maternal brain has any physiological or pathophysiological functional significance, fetomaternal microchimerism provides a novel model for the experimental investigation of the properties of fetal progenitor or stem cells in the brain without prior in vitro manipulation. Characterization of the properties of these cells that allow them to cross both the placental and blood–brain barriers and to target injured brain may improve selection procedures for isolation of progenitor or stem cells for brain repair by intravenous infusion.

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