Improving outcomes of acute kidney injury using mouse renal progenitor cells alone or in combination with erythropoietin or suramin

Stem Cell Res Ther. 2013 Jun 18;4(3):74. doi: 10.1186/scrt225.

Abstract

Introduction: So far, no effective therapy is available for acute kidney injury (AKI), a common and serious complication with high morbidity and mortality. Interest has recently been focused on the potential therapeutic effect of mouse adult renal progenitor cells (MRPC), erythropoietin (EPO) and suramin in the recovery of ischemia-induced AKI. The aim of the present study is to compare MRPC with MRPC/EPO or MRPC/suramin concomitantly in the treatment of a mouse model of ischemia/reperfusion (I/R) AKI.

Methods: MRPC were isolated from adult C57BL/6-gfp mice. Male C57BL/6 mice (eight-weeks old, n = 72) were used for the I/R AKI model. Serum creatinine (Cr), blood urea nitrogen (BUN) and renal histology were detected in MRPC-, MRPC/EPO-, MRPC/suramin- and PBS-treated I/R AKI mice. E-cadherin, CD34 and GFP protein expression was assessed by immunohistochemical assay.

Results: MRPC exhibited characteristics consistent with renal stem cells. The features of MRPC were manifested by Pax-2, Oct-4, vimentin, α-smooth muscle actin positive, and E-cadherin negative, distinguished from mesenchymal stem cells (MSC) by expression of CD34 and Sca-1. The plasticity of MRPC was shown by the ability to differentiate into osteoblasts and lipocytes in vitro. Injection of MRPC, especially MRPC/EPO and MRPC/suramin in I/R AKI mice attenuated renal damage with a decrease of the necrotic injury, peak plasma Cr and BUN. Furthermore, seven days after the injury, MRPC/EPO or MRPC/suramin formed more CD34(+) and E-cadherin+ cells than MRPC alone.

Conclusions: These results suggest that MRPC, in particular MRPC/EPO or MRPC/suramin, promote renal repair after injury and may be a promising therapeutic strategy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / drug therapy
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / therapy*
  • Adult Stem Cells / cytology
  • Adult Stem Cells / metabolism
  • Adult Stem Cells / transplantation*
  • Animals
  • Antigens, CD34 / metabolism
  • Cadherins / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Drug Therapy, Combination
  • Epoetin Alfa
  • Erythropoietin / therapeutic use*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Hematinics / therapeutic use*
  • Kidney / cytology*
  • Kidney / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Octamer Transcription Factor-3 / metabolism
  • PAX2 Transcription Factor / metabolism
  • Recombinant Proteins / therapeutic use
  • Suramin / therapeutic use*
  • Vimentin / metabolism

Substances

  • Antigens, CD34
  • Cadherins
  • Hematinics
  • Octamer Transcription Factor-3
  • PAX2 Transcription Factor
  • Pax2 protein, mouse
  • Pou5f1 protein, mouse
  • Recombinant Proteins
  • Vimentin
  • Erythropoietin
  • Green Fluorescent Proteins
  • Suramin
  • Epoetin Alfa