The effects of therapeutic concentrations of gentamicin, amikacin and hyaluronic acid on cultured bone marrow-derived equine mesenchymal stem cells.

Abstract

REASONS FOR PERFORMING STUDY: 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. STUDY DESIGN: 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. CONCLUSION: 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. POTENTIAL RELEVANCE: Based on these findings, the mixing of aminoglycoside antimicrobials and cultured equine BM-MSCs prior to therapeutic use is not recommended.