The cellular origin and proliferative status of regenerating renal parenchyma after mercuric chloride damage and erythropoietin treatment.
OBJECTIVE
In this study, we have sought to establish the cellular origin and proliferative status of the renal parenchyma as it regenerates after damage induced by mercuric chloride, with or without erythropoietin treatments, that might alter the response.


METHODS
Female mice were irradiated and male whole bone marrow was transplanted into them. Six weeks later recipient mice were assigned to one of four groups: control, mercuric chloride treated, erythropoietin treated and treated with mercuric chloride plus erythropoietin.


RESULTS
Tubular injury scores were high 3 days after mercuric chloride and had recovered partially after 14 days, in line with serum urea nitrogen levels. Confocal microscopy confirmed the tubular location of bone marrow-derived cells. A 'four-in-one' analytical technique (identifying cell origin, tubular phenotype, tubular basement membranes and S-phase status) revealed that tubular necrosis increased bone marrow derivation of renal tubular epithelium from a baseline of approximately 1.3% to approximately 4.0%. Erythropoietin increased the haematocrit, but no other effects were detected.


CONCLUSIONS
As 1 in 12 proximal tubular cells in S-phase was derived from bone marrow, we conclude that in the kidney, the presence of bone marrow-derived cells makes a minor but important regenerative contribution after tubular necrosis.
Yen
T-H
TH
Histopathology Unit, Cancer Research UK, London Research Institute, London, UK.
Alison
M R
MR
Cook
H T
HT
Jeffery
R
R
Otto
W R
WR
Wright
N A
NA
Poulsom
R
R
D019264:Adoptive Transfer; D000818:Animals; D001806:Blood Urea Nitrogen; D001854:Bone Marrow Cells / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D006400:Hematocrit; D006410:Hematopoiesis / Q000187:drug effects; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced / Q000473:pathology*; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins; D012038:Regeneration / Q000187:drug effects*; D013936:Thymidine; D013997:Time Factors
D011994:Recombinant Proteins; D004921:Erythropoietin; D008627:Mercuric Chloride; D004247:DNA; D013936:Thymidine