title: The effects of therapeutic concentrations of gentamicin, amikacin and hyaluronic acid on cultured bone marrow-derived equine mesenchymal stem cells.
abstract: BACKGROUND
  Joint inflammation and septic arthritis are both potential complications of intra-articular injections of bone marrow-derived mesenchymal stem cells (BM-MSCs). Clinicians may prophylactically co-inject BM-MSCs admixed with either antimicrobials or hyaluronic acid; however, the effect of these agents on cultured BM-MSCs is unknown.
  
  
  OBJECTIVE
  To determine the effects of therapeutic levels of gentamicin, amikacin and hyaluronic acid on cultured equine BM-MSCs in vitro.
  
  
  METHODS
  In vitro experimental study.
  
  
  METHODS
  Equine BM-MSCs from 4 healthy mature horses were isolated. Cultured BM-MSCs from each donor were incubated with gentamicin (150 mg), amikacin (250 mg), hyaluronic acid (22 mg) or 1% penicillin/streptomycin (control) under sterile conditions. Mesenchymal stem cells viability, proliferation, mediator secretion and culture media pH were measured.
  
  
  RESULTS
  Incubation of BM-MSCs with gentamicin resulted in >95% MSC death after 45 min, and incubation of BM-MSCs with amikacin resulted in >95% MSC death after 2 h. Incubation of BM-MSCs with hyaluronic acid or penicillin/streptomycin (control) for up to 6 h resulted in sustained BM-MSC viability of 80% and >93%, respectively. All additives resulted in decreased media pH in the first minute; however, the pH then remained constant over the 6 h incubation period. No significant differences in BM-MSC proliferation or mediator secretion between the penicillin/streptomycin (control) and cells treated with hyaluronic acid were observed.
  
  
  CONCLUSIONS
  Therapeutic concentrations of aminoglycoside antimicrobials are toxic to cultured equine BM-MSCs. The effects of hyaluronic acid on cultured MSC viability, proliferation and mediator secretion are minimal.
  
  
  CONCLUSIONS
  Based on these findings, the mixing of aminoglycoside antimicrobials and cultured equine BM-MSCs prior to therapeutic use is not recommended.
authors: Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, USA.
authors: L K
authors: LK
authors: Bohannon
authors: S D
authors: SD
authors: Owens
authors: N J
authors: NJ
authors: Walker
authors: D D
authors: DD
authors: Carrade
authors: L D
authors: LD
authors: Galuppo
authors: D L
authors: DL
authors: Borjesson
mesh_terms: D000583:Amikacin / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005839:Gentamicins / Q000008:administration & dosage / Q000494:pharmacology*; D006736:Horses; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008264:Macrophages / Q000187:drug effects*; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D055675:Viscosupplements / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D055675:Viscosupplements; D000583:Amikacin; D006820:Hyaluronic Acid
keywords: antimicrobials; bone marrow; cell culture; cytotoxicity; horse; mesenchymal stem cell