Experimental model
Effect of Whole Bone Marrow Cell Infusion in the Progression of Experimental Chronic Renal Failure

https://doi.org/10.1016/j.transproceed.2008.03.009Get rights and content

Abstract

Introduction

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 × 106 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.

Conclusion

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.

Section snippets

Materials and Methods

Animal procedures were performed in accordance with protocols approved by our Animal Care and Use Committee. Fifteen adult male Wistar rats (250 to 300 g) underwent 5/6 renal mass reduction as previously described.3 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. Bone marrow cells isolated from femoral and tibial bones of Wistar rats were separated into mononuclear

Results

sCr at baseline was 0.43 ± 0.04 mg/dL in the control group, 0.43 ± 0.05 mg/dL in the MoSC group, and 0.5 ± 0.1 mg/dL in the MSC group (Table 1). At 120 days, sCr values were 1.31 ± 0.5 mg/dL (control), 0.81 ± 0.2 mg/dL (MoSC), and 0.95 ± 0.1 mg/dL (MSC) (P = NS). The percentages of increase in sCr at day 120 versus the baseline levels were: 205% (control), 81% (MoSC), and 97.5% (MSC). Baseline values of Clcr did not vary significantly among the groups (control = 1.23 ± 0.33 mL/min; MoSC = 1.14

Discussion

Stem cell therapy has been used to repair injuries in liver, heart, and brain models. Reports have shown that bone marrow stem cells contribute to the repair of acutely damaged kidneys.7 Our results showed that injection of MoSCs or MSCs may have an effect on the CRF induced in rats because after 120 days treated animals showed a increase in sCr at least two times lower than untreated rats. In addition, the rate of progression of CRF, measured by the decline in Clcr, was significantly reduced

References (7)

There are more references available in the full text version of this article.

Cited by (0)

This work was supported in part by the FAMERP-BAP/FUNFARME and Braile Biomédica.

View full text