Determinants of tubular bone marrow-derived cell engraftment after renal ischemia/reperfusion in rats.
BACKGROUND
Ischemia/reperfusion (I/R) injury is a major cause of acute renal failure (ARF). ARF is reversible, due to an innate regenerative process, which is thought to depend partly on bone marrow-derived progenitor cells. The significance of these cells in the repair process has been questioned in view of their relatively low frequency. Here, we hypothesize that the severity of renal damage and the postischemic recovery time are determinants of tubular bone marrow-derived cell (BMDC) engraftment.


METHODS
We used a model of unilateral renal I/R in F344 rats reconstituted with R26-human placental alkaline phosphatase (hPAP) transgenic bone marrow, in which we quantified and characterized tubular BMDC engraftment with increasing severity of damage and in time.


RESULTS
After I/R injury, BMDC engrafted the tubular epithelium and acquired an epithelial phenotype. Tubular epithelial BMDC engraftment increased with longer ischemic time, indicating that tubular epithelial BMDC engraftment increases with the severity of damage. The number of circulating progenitor cells doubled early after I/R injury and was followed by a transient increase in tubular epithelial BMDC engraftment. The latter positively correlated with morphological recovery of the kidney over time. CONCLUSION. The extent of tubular BMDC engraftment depends on the severity of renal damage and follows a distinct time course after I/R injury. Therefore, the severity of damage and time course need to be taken into account when interpreting data on the role of tubular BMDC engraftment in renal repair after I/R injury.
Broekema
Martine
M
Department of Pathology and Laboratory Medicine, Medical Biology Section, University Medical Center Groningen, Univerisity of Groningen, The Netherlands. m.broekema@med.umcg.nl
Harmsen
Martin C
MC
Koerts
Jasper A
JA
Petersen
Arjen H
AH
van Luyn
Marja J A
MJ
Navis
Gerjan
G
Popa
Eliane R
ER
D058186:Acute Kidney Injury / Q000473:pathology* / Q000628:therapy*; D000818:Animals; D000963:Antimetabolites; D016026:Bone Marrow Transplantation / Q000379:methods*; D001973:Bromodeoxyuridine; D004847:Epithelial Cells / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology / Q000502:physiology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D020127:Recovery of Function; D012038:Regeneration; D015427:Reperfusion Injury / Q000473:pathology* / Q000628:therapy*; D012720:Severity of Illness Index
D000963:Antimetabolites; D001973:Bromodeoxyuridine