Tubular engraftment and myofibroblast differentiation of recipient-derived cells after experimental kidney transplantation.
BACKGROUND
In human renal allografts, recipient-derived cells engrafted in various kidney substructures, have been detected in the long term after transplantation. Here we investigated tubular engraftment and myofibroblast differentiation of recipient-derived cells at short term after experimental kidney transplantation, during a previously described window of regeneration and possible onset of renal interstitial fibrosis.


METHODS
Fisher (F344, syngeneic) and Dark Agouti (DA, allogeneic) kidneys were transplanted into F344-hPAP transgenic recipient rats, which allowed tracing of recipient-derived cells in nontransgenic donor kidneys. We evaluated tubular engraftment and myofibroblast differentiation of recipient-derived cells on day 14 after kidney transplantation.


RESULTS
Kidney transplantation resulted in tubular engraftment of recipient-derived cells. After allogeneic kidney transplantation, 9.7% of tubular cross-sections contained at least one recipient-derived cell, which represented a significant increase in comparison to syngeneic transplantation (4.0%, P<0.05). Moreover, recipient-derived myofibroblasts were present in the renal interstitium of the transplanted kidney. These cells contributed 39% of the total interstitial myofibroblast population in allografts, which was comparable to the syngeneic situation (28%, P=0.25).


CONCLUSIONS
In a defined early window of regeneration and possible onset of renal interstitial fibrosis after kidney transplantation, rejection-associated injury, superimposed on ischemic damage, increases tubular engraftment of recipient-derived cells, although it does not affect their relative contribution to the renal interstitial myofibroblast population.
Broekema
Martine
M
Department of Pathology & Laboratory Medicine, Medical Biology Section, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Harmsen
Martin C
MC
Koerts
Jasper A
JA
van Kooten
Theo G
TG
Navis
Gerjan
G
van Luyn
Marja J A
MJ
Popa
Eliane R
ER
D000469:Alkaline Phosphatase / Q000032:analysis / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation; D024061:Collagen Type III / Q000032:analysis; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D005355:Fibrosis; D006084:Graft Rejection / Q000209:etiology* / Q000473:pathology*; D007511:Ischemia / Q000473:pathology; D007668:Kidney / Q000098:blood supply / Q000473:pathology / Q000502:physiology; D016030:Kidney Transplantation / Q000473:pathology*; D007684:Kidney Tubules / Q000473:pathology* / Q000502:physiology; D008297:Male; D023421:Models, Animal; D032446:Myoblasts / Q000166:cytology / Q000201:enzymology; D051381:Rats; D012038:Regeneration
D024061:Collagen Type III; D000469:Alkaline Phosphatase