Effect of whole bone marrow cell infusion in the progression of experimental chronic renal failure.
BACKGROUND
The therapeutic potential of adult stem cells for the treatment of chronic diseases is becoming increasingly evident over the last few years. In the present study, we sought to assess whether the infusion of bone marrow-derived mononuclear cells (MoSCs) and mesenchymal cells (MSCs) could reduce/stabilize the rate of progression of chronic renal failure (CRF) in rats.


METHODS
We used the 5/6 renal mass reduction model to induce chronic renal failure in male Wistar rats. Renal function was assessed by measurements of serum creatinine (sCr), creatinine clearance (Clcr), and 24-hour proteinuria at baseline as well as 60 and 120 days after surgery. MoSCs and MSCs obtained from bone marrow aspirates were separated by the Ficoll-Hypaque method. After a 12- to 14-day culture, 1.5 x 10(6) MSCs and the same number of MoSCs were injected into the renal parenchyma of the remanant kidney of rats with CRF on the day of surgery.


RESULTS
Among the control group, at day 120, the results were sCr = 1.31 +/- 0.5 mg/dL, Clcr = 0.64 +/- 0.35 mL/min, and proteinuria = 140.0 +/- 57.7 mg/24 h. Rats treated with MoSCs at day 120 had sCr = 0.81 +/- 0.20 mg/dL, Clcr = 1.05 +/- 0.26 mL/min, and proteinuria = 61 +/- 46.5 mg/24 h, while rats injected with MSCs had sCr = 0.95 +/- 0.1 mg/dL, Clcr = 0.68 +/- 0.24 mL/min, and proteinuria = 119.2 +/- 50.0 mg/24 h. Analysis of the progression to CRF showed that the treatment significantly reduced the rate of decline in Clcr after treatment with MoSc: control: -0.0049 +/- 0.0024 mL/min/d versus MSC: - 0.0013 +/- 0.0017 mL/min/d versus MoSC: +0.0002 +/- 0.0016 mL/min/d (P = .017). Proteinuria tended to be lower among the treated groups. Histological scores of chronic damage were not different, but distinct patterns of chronic lesions were observed among treated rats.


CONCLUSIONS
Our results showed that progression of CRF in rats could be slowed/stabilized by intrarenal parenchymal injection of MoSCs. A trend toward reduction in the progression rate of CRF was also observed with injection of MSCs.
Caldas
H C
HC
Laboratory of Immunology and Experimental Transplantation-LITEX, Medical School-FAMERP/FUNFARME, São José do Rio Preto, SP, Brazil.
Fernandes
I M M
IM
Gerbi
F
F
Souza
A C
AC
Baptista
M A S F
MA
Ramalho
H J
HJ
Kawasaki-Oyama
R S
RS
Goloni-Bertollo
E M
EM
Pavarino-Bertelli
E C
EC
Braile
D M
DM
Abbud-Filho
M
M
D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods; D003404:Creatinine / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D007676:Kidney Failure, Chronic / Q000601:surgery*; D017708:Leukocyte Transfusion; D007963:Leukocytes, Mononuclear; D008297:Male; D008648:Mesoderm / Q000166:cytology / Q000637:transplantation; D051381:Rats; D017208:Rats, Wistar
D003404:Creatinine