Donor and recipient origin of mesenchymal and endothelial cells in chronic renal allograft remodeling.
Chronic transplant dysfunction (CTD) is the leading cause for limited kidney graft survival. Renal CTD is characterized by interstitial and vascular remodeling leading to interstitial fibrosis, tubular atrophy and transplant vasculopathy (TV). The origin of cells and pathogenesis of interstitial and vascular remodeling are still unknown. To study graft-versus-recipient origin of interstitial myofibroblasts, vascular smooth muscle cells (SMCs) and endothelial cells (ECs), we here describe a new rat model for renal CTD using Dark Agouti kidney donors and R26 human placental alkaline phosphatase transgenic Fischer344 recipients. This model showed the development of CTD within 12 weeks after transplantation. In interstitial remodeling, both graft- and recipient-derived cells contributed to a similar extent to the accumulation of myofibroblasts. In arteries with TV, we observed graft origin of neointimal SMCs and ECs, whereas in peritubular and glomerular capillaries, we detected recipient EC chimerism. These data indicate that, within the interstitial and vascular compartments of the transplanted kidney, myofibroblasts, SMCs and ECs involved in chronic remodeling are derived from different sources and suggest distinct pathogenetic mechanisms within the renal compartments.
Rienstra
H
H
Department of Cell Biology, Immunology Section, University Medical Center Groningen, Groningen, The Netherlands.
Boersema
M
M
Onuta
G
G
Boer
M W
MW
Zandvoort
A
A
van Riezen
M
M
Rozing
J
J
van Goor
H
H
Navis
G J
GJ
Popa
E R
ER
Hillebrands
J L
JL
D000818:Animals; D002908:Chronic Disease; D024042:Collagen Type I / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006085:Graft Survival / Q000276:immunology; D007674:Kidney Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000276:immunology
D024042:Collagen Type I