Biphasic recruitment of microchimeric fetal mesenchymal cells in fibrosis following acute kidney injury

Roy, Edwige, Seppanen, Elke, Ellis, Rebecca, Lee, Eddy S., Khosroterani, Kiarash, Fisk, Nicholas M. and Bou-Gharios, George (2014) Biphasic recruitment of microchimeric fetal mesenchymal cells in fibrosis following acute kidney injury. Kidney International, 85 3: 600-610. doi:10.1038/ki.2013.459


Author Roy, Edwige
Seppanen, Elke
Ellis, Rebecca
Lee, Eddy S.
Khosroterani, Kiarash
Fisk, Nicholas M.
Bou-Gharios, George
Title Biphasic recruitment of microchimeric fetal mesenchymal cells in fibrosis following acute kidney injury
Journal name Kidney International   Check publisher's open access policy
ISSN 0085-2538
1523-1755
Publication date 2014-03
Year available 2013
Sub-type Article (original research)
DOI 10.1038/ki.2013.459
Volume 85
Issue 3
Start page 600
End page 610
Total pages 11
Place of publication London, United Kingdom
Publisher Nature
Collection year 2014
Language eng
Formatted 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.
Keyword Aristolochic acid
Fetal microchimerism
Mesenchymal cells
Nephropathy
Renal interstitial fibrosis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2014 Collection
 
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