Donor and Recipient Origin of Mesenchymal and Endothelial Cells in Chronic Renal Allograft Remodeling

H. Rienstra, M. Boersema, G. Onuta, M. W. Boer, A. Zandvoort, M. van Riezen, J. Rozing, H. van Goor, G. J. Navis, E. R. Popa, J. L. Hillebrands*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)463-472
Number of pages10
JournalAmerican Journal of Transplantation
Volume9
Issue number3
DOIs
Publication statusPublished - Mar-2009

Keywords

  • Chronic transplant dysfunction
  • endothelial cells
  • interstitial fibrosis
  • myofibroblasts
  • smooth muscle cells
  • transplant vasculopathy
  • SMOOTH-MUSCLE-CELLS
  • EXPERIMENTAL KIDNEY-TRANSPLANTATION
  • PROGENITOR CELLS
  • STEM-CELLS
  • CEREBROSPINAL-FLUID
  • BONE-MARROW
  • ARTERIOSCLEROSIS
  • CHIMERISM
  • RAT
  • REJECTION

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