Caldas H C, Fernandes I M M, Gerbi F, Souza A C, Baptista M A S F, Ramalho H J, Kawasaki-Oyama R S, Goloni-Bertollo E M, Pavarino-Bertelli E C, Braile D M, Abbud-Filho M
Laboratory of Immunology and Experimental Transplantation-LITEX, Medical School-FAMERP/FUNFARME, São José do Rio Preto, SP, Brazil.
Transplant Proc. 2008 Apr;40(3):853-5. doi: 10.1016/j.transproceed.2008.03.009.
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.
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.
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.
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.
在过去几年中，成体干细胞治疗慢性疾病的潜力日益明显。在本研究中，我们试图评估输注骨髓来源的单个核细胞（MoSCs）和间充质细胞（MSCs）是否能降低/稳定大鼠慢性肾衰竭（CRF）的进展速度。
我们采用5/6肾切除模型诱导雄性Wistar大鼠发生慢性肾衰竭。在基线以及术后60天和120天，通过测量血清肌酐（sCr）、肌酐清除率（Clcr）和24小时蛋白尿来评估肾功能。通过Ficoll-Hypaque方法分离从骨髓抽吸物中获得的MoSCs和MSCs。经过12至14天的培养后，在手术当天将1.5×10⁶个MSCs和相同数量的MoSCs注射到患有CRF的大鼠残余肾的肾实质中。
在对照组中，第120天时，结果为sCr = 1.31±0.5mg/dL，Clcr = 0.64±0.35mL/min，蛋白尿 = 140.0±57.7mg/24h。在第120天接受MoSCs治疗的大鼠sCr = 0.81±0.20mg/dL，Clcr = 1.05±0.26mL/min，蛋白尿 = 61±46.5mg/24h，而注射MSCs的大鼠sCr = 0.95±0.1mg/dL，Clcr = 0.68±0.24mL/min，蛋白尿 = 119.2±50.0mg/24h。对CRF进展的分析表明，治疗后MoSc治疗组显著降低了Clcr的下降速度：对照组：-0.0049±0.0024mL/min/d，MSCs组：-0.0013±0.0017mL/min/d，MoSCs组：+0.0002±0.0016mL/min/d（P = 0.017）。治疗组中的蛋白尿倾向于更低。慢性损伤的组织学评分没有差异，但在治疗的大鼠中观察到了不同的慢性病变模式。
我们的结果表明，通过肾实质内注射MoSCs可减缓/稳定大鼠CRF的进展。注射MSCs也观察到CRF进展速度降低的趋势。
