Donor and recipient contribution to transplant vasculopathy in chronic renal transplant dysfunction.
BACKGROUND
Chronic transplant dysfunction is the leading cause of long-term renal allograft loss. One of the histologic hallmarks of chronic transplant dysfunction is transplant vasculopathy characterized by accumulation of smooth muscle cells (SMCs) in the arterial subendothelial space, leading to ischemic graft failure. Currently, no therapy is available for transplant vasculopathy, and knowledge of the origin (donor vs. recipient) of neointimal cells may contribute to develop adequate strategies.


METHODS
Origin of neointimal SMCs, endothelial, and tubular cells was determined in four nephrectomy samples from male recipients transplanted with a female kidney. Recipient-derived cells were detected using X- and Y-chromosome-specific fluorescent in situ hybridization combined with immunofluorescent staining. Specificity and sensitivity of fluorescent in situ hybridization were determined with corresponding controls.


RESULTS
No Y-chromosome-positive cells were detected in the female to female graft, whereas approximately 31% of nucleated cells in male to male grafts had a detectable Y-chromosome. In female to male grafts, a recipient-derived population of neointimal alpha-smooth muscle actin-positive SMCs were detected (6%, range 3%-11%). Percentages of recipient-derived arterial endothelial cells, glomerular endothelial cells, and tubular epithelial cells were 14% (range 4%-32%), 19% (range 7%-31%) and 3% (range 2%-5%), respectively.


CONCLUSIONS
Both donor- and recipient-derived cells contribute to vascular remodeling in clinical renal transplantation. The presence of alpha-smooth muscle actin in donor- and recipient-derived cells supports a constructive role for these cells in neointimal formation. However, the predominance of donor-derived cells in the neointima points to these cells as the likely therapeutic target.
Boersema
Miriam
M
Department of Pathology and Medical Biology, Division of Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Rienstra
Heleen
H
van den Heuvel
Marius
M
van Goor
Harry
H
van Luyn
Marja J A
MJ
Navis
Gerjan J
GJ
Popa
Eliane R
ER
Hillebrands
Jan-Luuk
JL
D000328:Adult; D000368:Aged; D002908:Chronic Disease; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology*; D006085:Graft Survival; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007511:Ischemia / Q000276:immunology / Q000473:pathology*; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation / Q000379:methods*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009389:Neovascularization, Pathologic