Mesenchymal stem cells in renal function recovery after acute kidney injury: use of a differentiating agent in a rat model

Cell Transplant. 2011;20(8):1193-208. doi: 10.3727/096368910X543394. Epub 2010 Nov 19.

Abstract

Acute kidney injury (AKI) is a major health care condition with limited current treatment options. Within this context, stem cells may provide a clinical approach for AKI. Moreover, a synthetic compound previously developed, hyaluronan monoesters with butyric acid (HB), able to induce metanephric differentiation, formation of capillary-like structures, and secretion of angiogenic cytokines, was tested in vitro. Thereafter, we investigated the effects of human mesenchymal stem cells from fetal membranes (FMhMSCs), both treated and untreated with HB, after induction of ischemic AKI in a rat model. At reperfusion following 45-min clamping of renal pedicles, each rat was randomly assigned to one of four groups: CTR, PBS, MSC, and MSC-HB. Renal function at 1, 3, 5, and 7 days was assessed. Histological samples were analyzed by light and electron microscopy and renal injury was graded. Cytokine analysis on serum samples was performed. FMhMSCs induced an accelerated renal functional recovery, demonstrated by biochemical parameters and confirmed by histology showing that histopathological alterations associated with ischemic injury were less severe in cell-treated kidneys. HB-treated rats showed a minor degree of inflammation, both at cytokine and TEM analyses. Better functional and morphological recovery were not associated to stem cells' regenerative processes, but possibly suggest paracrine effects on microenvironment that induce retrieval of renal damaged tissues. These results suggest that FMhMSCs could be useful in the treatment of AKI and the utilization of synthetic compounds could enhance the recovery induction ability of cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / blood
  • Acute Kidney Injury / physiopathology*
  • Acute Kidney Injury / therapy*
  • Animals
  • Butyric Acid / pharmacology
  • Cell Differentiation* / drug effects
  • Cytokines / blood
  • Disease Models, Animal
  • Humans
  • Hyaluronic Acid / pharmacology
  • Immunohistochemistry
  • Kidney / drug effects
  • Kidney / pathology
  • Kidney / physiopathology
  • Kidney / ultrastructure
  • Kidney Function Tests*
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / ultrastructure
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects
  • Recovery of Function / physiology*

Substances

  • Cytokines
  • Butyric Acid
  • Hyaluronic Acid