CD34+ cells in maternal placental blood are mainly fetal in origin and express endothelial markers

Abstract

Fetal CD34 þ cells enter the maternal circulation during pregnancy and may persist for decades. These cells are usually depicted as hematopoietic stem/progenitor cells. Our objective was to further determine the phenotype of fetal chimeric CD34 þ cells in placental maternal blood from the intervillous space (IVS). Human healthy term placentas were analyzed (n ¼ 9). All fetuses were male. CD34 þ cells were identified in the IVS and further characterized as fetal or maternal using X and Y chromosome fluorescence in situ hybridization. The phenotype of fetal cells was further analyzed using anti-CD117 (c-kit), anti-CD133, anti-CD31, anti-von Willebrand factor (vWF), anti-vimentin, anti-CD45 and anticytokeratin (CK) antibodies. We used preeclamptic placentas of male (n ¼ 3) and healthy placentas of female fetuses (n ¼ 3) as controls. As expected fetal cells were easily identified in the IVS and significantly increased in cases of preeclampsia. Most CD34 þ cells in the IVS were of fetal origin (90%) and were not surrounded by CK staining further showing that they were not in fetal trophoblastic villi. Similarly, about 40% of CD31 þ and 6% of vimentin þ cells in the IVS were fetal in origin. No CD117 þ or CD133 þ fetal cells were found in the IVS of examined placentas. Besides, all the CD34 þ cells identified in the IVS were co-labeled with vWF or CD31, suggesting their endothelial origin. These results suggest that most CD34 þ cells in maternal placental blood at term are fetal in origin from endothelial and not hematopoietic lineages.

Microchimeric Fetal Cells Are Recruited to Maternal Kidney following Injury and Activate Collagen Type I Transcription

“…Small numbers of fetal cells traffic across the mammalian placenta into the maternal circulation in every pregnancy [Jackson, 2003;Jimenez et al, 2005;Bianchi and Fisk, 2007;Parant et al, 2009]. Increasing evidence suggests that fetal microchimeric cells (FMCs) engraft and persist lifelong in most women [O'Donoghue et al, 2004].…”

“…Notwithstanding this, other evidence implicates cells of haemopoietic origin, given the phenotype of FMCs in maternal blood years after pregnancy [Bianchi et al, 1996;Evans et al, 1999], the finding of CD45+ FMCs in healthy post-partum tissues [Khosrotehrani et al, 2004], and experimental data implicating FMCs in liver repair and functional fetal lymphoid progenitors in the mother . More recent evidence implicates endothelial cells, as fetal endothelial progenitor cells make up most of the CD34+ cells in maternal intervillous blood [Parant et al, 2009], and experimentally participate in angiogenesis in maternal inflammatory [Nguyen Huu et al, 2007] and tumour sites [Nguyen Huu et al, 2009].…”

Fetal microchimeric cells in autoimmune thyroid diseases

“…These cells were termed pregnancy-associated progenitor cells (PAPCs) 20 . Many authors described the transfer of fetal hematopoietic progenitor cells, 27 , 48 fetal mesenchymal stem cells 49 , 50 or endothelial progenitor cells 51 to the mother. They can represent a long-term reservoir of stem cells with multilineage potential 47 , 52 …”

Fetal microchimerism in skin wound healing

“…These findings along with previous reports, including ours, converge toward the presence of fetal EPCs among the transferred FMCs. 11,12,18,19 Two important questions that we addressed were as follows: were FMCs recruited in high numbers de novo or did randomly transferred FMCs proliferate in situ after tissue injury? Did fetal EPCs respond to specific chemotactic and angiogenic signals as their maternal counterparts?…”