Amniotic fluid-derived mesenchymal stem cells prevent fibrosis and preserve renal function in a preclinical porcine model of kidney transplantation

Stem Cells Transl Med. 2014 Jul;3(7):809-20. doi: 10.5966/sctm.2013-0186. Epub 2014 May 5.

Abstract

It is well known that ischemia/reperfusion injuries strongly affect the success of human organ transplantation. Development of interstitial fibrosis and tubular atrophy is the main deleterious phenomenon involved. Stem cells are a promising therapeutic tool already validated in various ischemic diseases. Amniotic fluid-derived mesenchymal stem cells (af-MSCs), a subpopulation of multipotent cells identified in amniotic fluid, are known to secrete growth factors and anti-inflammatory cytokines. In addition, these cells are easy to collect, present higher proliferation and self-renewal rates compared with other adult stem cells (ASCs), and are suitable for banking. Consequently, af-MSCs represent a promising source of stem cells for regenerative therapies in humans. To determine the efficiency and the safety of af-MSC infusion in a preclinical porcine model of renal autotransplantation, we injected autologous af-MSCs in the renal artery 6 days after transplantation. The af-MSC injection improved glomerular and tubular functions, leading to full renal function recovery and abrogated fibrosis development at 3 months. The strong proof of concept generated by this translational porcine model is a first step toward evaluation of af-MSC-based therapies in human kidney transplantation.

Keywords: Amniotic fluid-derived mesenchymal stem cells; Deceased after cardiac arrest donors; Ischemia reperfusion injury; Kidney transplantation; Pig; Preclinical model.

MeSH terms

  • Amniotic Fluid / cytology*
  • Animals
  • Cell Tracking
  • Cells, Cultured
  • Female
  • Fibrosis
  • Graft Survival
  • Green Fluorescent Proteins / biosynthesis
  • Green Fluorescent Proteins / genetics
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney / physiopathology
  • Kidney / surgery*
  • Kidney Transplantation / adverse effects*
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells* / metabolism
  • Multipotent Stem Cells / metabolism
  • Multipotent Stem Cells / transplantation*
  • Pregnancy
  • Recovery of Function
  • Reperfusion Injury / etiology
  • Reperfusion Injury / pathology
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control*
  • Swine
  • Time Factors
  • Transduction, Genetic
  • Transfection / methods
  • Transplantation, Autologous

Substances

  • Green Fluorescent Proteins