title: Fetal progenitor cells naturally transferred through pregnancy participate in inflammation and angiogenesis during wound healing.
abstract: The phenotype and fate of fetal microchimeric cells transfered into the maternal circulation during pregnancy are not well described. Since progenitors from distal sites mobilize during wound healing, we analyzed the recruitment and plasticity of fetal progenitors into maternal wounds. Wounds were generated on normal and bleomycin-induced fibrotic skin of parous or pregnant wild-type females with fluorescent GFP(+) fetuses. Analyses were performed on skin and blood specimens through PCR, immunohistochemistry, and flow cytometry. Controls consisted of parous and pregnant females without wounds and virgin females with wounds. Fetal cells were detected in all skin specimens of parous mice as long as healing was not achieved. During early stages of wound healing, fetal cells expressed mainly leukocyte markers, while in later phases endothelial markers prevailed. Fetally derived vessels connected to maternal circulation were also found, demonstrating the transfer of fetal endothelial progenitor cells. Wounding mobilized fetal CD34(+)ckit(-) cells into the blood during pregnancy. Most of this population was CD11b(-)VEGFR2(-). Another part was CD11b(+) with a fraction expressing VEGFR2. VEGFa-spiked Matrigel plugs partially mimicked this fetal progenitor recruitment and mobilization into the blood. In summary, fetal cells that mobilize in response to wounding are mainly progenitor cells and participate in angiogenesis and inflammation.
authors.affiliation: Université Pierre et Marie Curie, Laboratoire des Cellules Souches Fœtales, Paris, France. dany.nassar@inserm.fr
authors.forename: Dany
authors.initials: D
authors.lastname: Nassar
authors.forename: Catherine
authors.initials: C
authors.lastname: Droitcourt
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Mathieu-d'Argent
authors.forename: Min Ji
authors.initials: MJ
authors.lastname: Kim
authors.forename: Kiarash
authors.initials: K
authors.lastname: Khosrotehrani
authors.forename: Selim
authors.initials: S
authors.lastname: Aractingi
mesh_terms: D000818:Animals; D002633:Chemotaxis / Q000502:physiology; D046528:Chimerism / Q000196:embryology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011247:Pregnancy; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000166:cytology / Q000293:injuries; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D049452:Green Fluorescent Proteins