Combined Therapy With Adipose-Derived Mesenchymal Stem Cells and Ciprofloxacin Against Acute Urogenital Organ Damage in Rat Sepsis Syndrome Induced by Intrapelvic Injection of Cecal Bacteria

Stem Cells Transl Med. 2016 Jun;5(6):782-92. doi: 10.5966/sctm.2015-0116. Epub 2016 Apr 13.

Abstract

We hypothesized that combined treatment with autologous adipose-derived mesenchymal stem cell (ADMSC) and ciprofloxacin is superior to ciprofloxacin only in reducing sepsis-induced urogenital organ damage and mortality in rat sepsis syndrome (SS) caused by intrapelvic injection of cecal bacteria (1.0 × 10(4) cells per milliliter; total, 5.0 ml). Male Sprague-Dawley rats (n = 60) equally divided into group 1 (sham-control), group 2 (SS), group 3 (SS-ADMSC [5.0 × 10(5) intravenously at 0.5, 6, and 18 hours after sepsis induction]), group 4 (SS-ciprofloxacin [3.0 mg/kg, b.i.d.] for 5 days), and group 5 (SS-ADMSC-ciprofloxacin) were sacrificed by day 5. Mortality rate and creatinine level were highest in group 2 and lowest in group 1 and significantly higher in groups 3 and 4 than those in group 5, but there was no difference between groups 3 and 4 (all p < .005). The kidney injury score, inflammatory biomarker expressions at protein (tumor necrosis factor-1α, nuclear factor-κB, matrix metallopeptidase-9, regulated on activation, normal T-cell expressed and secreted, interleukin-1β) and cellular (CD14+, migratory inhibitor factor positive, CD68+) levels in kidneys and urinary bladder were lowest in group 1 and highest in group 2, higher in group 4 than in groups 3 and 5, and higher in group 3 than in group 5 (all p < .001). Protein expressions of apoptosis (Bax, cleaved caspase 3 and poly[ADP-ribose] polymerase 1, p21 protein [Cdc42/Rac]-activated kinase 2) and oxidative stress (oxidized protein, NADPH oxidase (NOX)-1, NOX-2) in these organs showed an identical pattern compared with that of inflammation in all groups (all p < .001). In conclusion, ADMSC-assisted ciprofloxacin therapy offered an additional benefit by reducing acute urogenital organ damage in rat.

Significance: Autologous adipose-derived mesenchymal stem cell-assisted ciprofloxacin therapy offered an additional benefit by reducing acute urogenital organ damage in rats.

Keywords: Adipose-derived mesenchymal stem cells; Antibiotics; Inflammation; Sepsis syndrome; Urogenital organ damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Animals
  • Apoptosis / drug effects
  • Bacteria / pathogenicity
  • Biomarkers / metabolism
  • Ciprofloxacin / administration & dosage
  • Disease Models, Animal
  • Humans
  • Inflammation / genetics
  • Inflammation / microbiology
  • Inflammation / pathology
  • Inflammation / therapy*
  • Kidney / drug effects
  • Kidney / injuries
  • Male
  • Male Urogenital Diseases / genetics
  • Male Urogenital Diseases / microbiology
  • Male Urogenital Diseases / pathology
  • Male Urogenital Diseases / therapy*
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Rats
  • Rats, Sprague-Dawley
  • Systemic Inflammatory Response Syndrome / genetics
  • Systemic Inflammatory Response Syndrome / microbiology
  • Systemic Inflammatory Response Syndrome / pathology
  • Systemic Inflammatory Response Syndrome / therapy*

Substances

  • Biomarkers
  • Ciprofloxacin