title: Biphasic recruitment of microchimeric fetal mesenchymal cells in fibrosis following acute kidney injury.
abstract: Fetal microchimeric cells (FMCs) enter the maternal circulation and persist in tissue for decades. They have capacity to home to injured maternal tissue and differentiate along that tissue's lineage. This raises the question of the origin(s) of cells transferred to the mother during pregnancy. FMCs with a mesenchymal phenotype have been documented in several studies, which makes mesenchymal stem cells an attractive explanation for their broad plasticity. Here we assessed the recruitment and mesenchymal lineage contribution of FMCs in response to acute kidney fibrosis induced by aristolochic acid injection. Serial in vivo bioluminescence imaging revealed a biphasic recruitment of active collagen-producing FMCs during the repair process of injured kidney in post-partum wild-type mothers that had delivered transgenic pups expressing luciferase under the collagen type I-promoter. The presence of FMCs long-term post injury (day 60) was associated with profibrotic molecules (TGF-β/CTGF), serum urea levels, and collagen deposition. Immunostaining confirmed FMCs at short term (day 15) using post-partum wild-type mothers that had delivered green fluorescent protein-positive pups and suggested a mainly hematopoietic phenotype. We conclude that there is biphasic recruitment to, and activity of, FMCs at the injury site. Moreover, we identified five types of FMC, implicating them all in the reparative process at different stages of induced renal interstitial fibrosis.
authors.affiliation: Experimental Dermatology Group, UQ Centre for Clinical Research, The University of Queensland, Herston Campus, Brisbane, Queensland, Australia.
authors.forename: Edwige
authors.initials: E
authors.lastname: Roy
authors.affiliation: Experimental Dermatology Group, UQ Centre for Clinical Research, The University of Queensland, Herston Campus, Brisbane, Queensland, Australia.
authors.forename: Elke
authors.initials: E
authors.lastname: Seppanen
authors.affiliation: Experimental Dermatology Group, UQ Centre for Clinical Research, The University of Queensland, Herston Campus, Brisbane, Queensland, Australia.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ellis
authors.affiliation: Experimental Dermatology Group, UQ Centre for Clinical Research, The University of Queensland, Herston Campus, Brisbane, Queensland, Australia.
authors.forename: Eddy S
authors.initials: ES
authors.lastname: Lee
authors.forename: Kiarash
authors.initials: K
authors.lastname: Khosrotehrani
authors.affiliation: Experimental Dermatology Group, UQ Centre for Clinical Research, The University of Queensland, Herston Campus, Brisbane, Queensland, Australia.
authors.forename: Kiarash
authors.initials: K
authors.lastname: Khosroterani
authors.affiliation: 1] Experimental Dermatology Group, UQ Centre for Clinical Research, The University of Queensland, Herston Campus, Brisbane, Queensland, Australia [2] Centre for Advanced Prenatal Care, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Fisk
authors.affiliation: 1] Experimental Dermatology Group, UQ Centre for Clinical Research, The University of Queensland, Herston Campus, Brisbane, Queensland, Australia [2] Institute of Ageing and Chronic Disease Musculoskeletal Biology, University of Liverpool, Liverpool, UK.
authors.forename: George
authors.initials: G
authors.lastname: Bou-Gharios
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology*; D000818:Animals; D002465:Cell Movement; D046528:Chimerism / Q000196:embryology*; D005260:Female; D005333:Fetus / Q000166:cytology*; D005355:Fibrosis; D006410:Hematopoiesis; D007668:Kidney / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000502:physiology; D008810:Mice, Inbred C57BL