Xenogeneic human umbilical cord-derived mesenchymal stem cells reduce mortality in rats with acute respiratory distress syndrome complicated by sepsis

Oncotarget. 2017 Jul 11;8(28):45626-45642. doi: 10.18632/oncotarget.17320.

Abstract

This study tested the hypothesis that xenogeneic human umbilical cord-derived mesenchymal stem cell (HUCDMSC) therapy would improve survival rates in rats with acute respiratory distress-syndrome (ARDS, induction by 48 h inhalation of 100% oxygen) and sepsis-syndrome (SS, induction by cecal-ligation and puncture) (ARDS-SS). Adult-male Sprague-Dawley rats were categorized into group 1 (sham-controls), group 2 (ARDS-SS), group 3 [ARDS-SS+HUCDMSC (1.2 ×106 cells administered 1 h after SS-induction)], and group 4 [ARDS-SS+HUCDMSC (1.2 ×106 cells administered 24 h after SS-induction)]. The mortality rate was higher in groups 2 and 4 than in groups 1 and 3 (all p<0.0001). The blood pressure after 28 h was lower in groups 2, 3 and 4 (p<0.0001) than in group 1. Albumin levels and percentages of inflammatory cells in broncho-alveolar lavage fluid, and the percentages of inflammatory and immune cells in circulation, were lowest in group 1, highest in group 2, and higher in group 3 than group 4 (all p<0.0001). The percentages of inflammatory cells in ascites and kidney parenchyma showed identical patterns, as did kidney injury scores (all p<0.0001). EarlyHUCDMSC therapy reduced rodent mortality after induced ARDS-SS.

Keywords: acute respiratory distress syndrome; inflammatory and immune reactions; mortality; sepsis syndrome; xenogeneic mesenchymal stem cell.

MeSH terms

  • Acute Kidney Injury / etiology
  • Animals
  • Apoptosis
  • Biomarkers
  • Blood Pressure
  • Cytokines / metabolism
  • Disease Models, Animal
  • Flow Cytometry
  • Heterografts
  • Humans
  • Inflammation Mediators / metabolism
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Oxidative Stress
  • Podocytes / metabolism
  • Rats
  • Respiratory Distress Syndrome / etiology*
  • Respiratory Distress Syndrome / mortality*
  • Respiratory Distress Syndrome / physiopathology
  • Respiratory Distress Syndrome / therapy
  • Sepsis / complications*
  • Umbilical Cord / cytology*
  • WT1 Proteins / genetics
  • WT1 Proteins / metabolism

Substances

  • Biomarkers
  • Cytokines
  • Inflammation Mediators
  • WT1 Proteins