The role of mesenchymal stem cells in the functional improvement of chronic renal failure

Stem Cells Dev. 2009 Apr;18(3):521-9. doi: 10.1089/scd.2008.0097.

Abstract

The most commonly used therapeutic targets in nephrology are the reduction of injury, the delay of progression, or renal replacement therapy. Many animal and human studies demonstrated the role of stem cells in repair and regenerations of kidney. Mesenchymal stem cells (MSCs) have shown to improve outcome of acute renal injury models. It is controversial whether MSCs can reduce injury following a toxic/ischemic event and delay renal failure in chronic kidney disease. We evaluated the hypothesis that the treatment with MSCs could improve renal function and attenuate injury in chronic renal failure (CRF). Sprague-Dawley female rats (8 weeks old, 182.2 +/- 7.2 g) underwent modified 5/6 nephrectomy. Rats in the MSC group received an injection of MSCs (1 x 10(6) cells) via tail vein 1 day after nephrectomy. Blood and urine samples were collected after 7 days and every month thereafter. The kidneys of rats were removed for histologic evaluation after 24-h urine collection and blood sampling. The Y-chromosome stain using fluorescent in situ hybridization was performed to verify the presence of male MSCs in the kidney of female recipients. No significant differences in blood urea nitrogen and creatinine concentration were observed between the MSC group and the untreated CRF group. However, the weight gain in the MSC group was greater than those in the CRF group after 4 months. Proteinuria in the MSC group was less than that in the CRF group over time. Y chromosome was detected in the kidney of MSC group. Although no significances were observed between these two groups, the histologic analysis suggests that MSCs have positive effect against glomerulosclerosis. These results suggest that MSCs help preserve renal function and attenuate renal injury in CRF.

MeSH terms

  • Animals
  • Blood Urea Nitrogen
  • Cell- and Tissue-Based Therapy*
  • Creatinine / urine
  • Disease Progression
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Kidney / cytology
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Failure, Chronic / physiopathology
  • Kidney Failure, Chronic / therapy*
  • Male
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / physiology*
  • Nephrectomy
  • Rats
  • Rats, Sprague-Dawley
  • Transforming Growth Factor beta / blood
  • Vascular Endothelial Growth Factor A / blood

Substances

  • Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A
  • Creatinine