Effects of mesenchymal stem cells transplanted at different time points in a rat remnant kidney model

Am J Nephrol. 2014;39(1):75-84. doi: 10.1159/000357870. Epub 2014 Jan 23.

Abstract

Aims: The optimal time for mesenchymal stem cell (MSCs) transplantation remains an unresolved issue. We compared the effects of MSCs on a rat remnant kidney model.

Methods: Male Sprague-Dawley rats were randomly divided and treated with a corresponding reagent at 4, 8, 12 and 16 weeks, respectively. A remnant kidney model was established and MSCs were injected into rats. The migration of MSCs was then assessed by using cell-tracking experiments. Renal function and histological analyses were performed 4 weeks after MSC transplantation. Immunohistochemistry, Western blotting and real-time polymerase chain reaction were used to detect the TGF-β1 and α-SMA levels.

Results: Four weeks after MSC injection, MSCs were found to migrate to the injured kidney. Significant histological damage improvement was observed after the treatment of MSCs at 4 and 8 weeks. The functional benefits of MSC treatment were observed in the 5/6 nephrectomy (Nx) + MSC group and the benefits were significantly higher at 4 and 8 weeks than at other time points (p < 0.05). Meanwhile, serum creatinine and urea levels as well as glomerular sclerosis and tubulointerstitial injury indexes were decreased at 4 and 8 weeks. Compared with the 5/6 Nx + PBS group, TGF-β1 and α-SMA levels were decreased in the 5/6 Nx + MSC group.

Conclusion: These data can be used to optimize the MSC transplantation time point as a therapeutic modality.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Cell Movement
  • Creatinine / blood
  • Fibrosis / therapy
  • Glomerular Filtration Rate
  • Glomerulosclerosis, Focal Segmental / blood
  • Kidney Transplantation / methods*
  • Kidney Tubules / injuries
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Transforming Growth Factor beta / metabolism
  • Urea / blood

Substances

  • Actins
  • Transforming Growth Factor beta
  • smooth muscle actin, rat
  • Urea
  • Creatinine

Supplementary concepts

  • Segmental glomerulosclerosis