Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, USA.
Equine Vet J. 2013 Nov;45(6):732-6. doi: 10.1111/evj.12045. Epub 2013 Feb 28.
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.
To determine the effects of therapeutic levels of gentamicin, amikacin and hyaluronic acid on cultured equine BM-MSCs in vitro.
In vitro experimental study.
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.
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.
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.
Based on these findings, the mixing of aminoglycoside antimicrobials and cultured equine BM-MSCs prior to therapeutic use is not recommended.
关节炎症和化脓性关节炎都是骨髓间充质干细胞(BM-MSCs)关节内注射的潜在并发症。临床医生可能会预防性地混合注射 BM-MSCs 与抗生素或透明质酸;然而,这些药物对培养的 BM-MSCs 的影响尚不清楚。
确定治疗浓度的庆大霉素、阿米卡星和透明质酸对体外培养的马 BM-MSCs 的影响。
体外实验研究。
从 4 匹健康成熟马中分离 BM-MSCs。从每个供体培养的 BM-MSCs 在无菌条件下与庆大霉素(150mg)、阿米卡星(250mg)、透明质酸(22mg)或 1%青霉素/链霉素(对照)孵育。测量间充质干细胞活力、增殖、介质分泌和培养基 pH。
BM-MSCs 与庆大霉素孵育 45 分钟后,超过 95%的 MSC 死亡;与阿米卡星孵育 2 小时后,超过 95%的 MSC 死亡。BM-MSCs 与透明质酸或青霉素/链霉素(对照)孵育长达 6 小时,分别保持 80%和>93%的 MSC 活力。所有添加剂在第 1 分钟内均导致培养基 pH 值降低;然而,在 6 小时孵育期间,pH 值保持不变。在 BM-MSC 增殖或介质分泌方面,青霉素/链霉素(对照)和用透明质酸处理的细胞之间没有显著差异。
治疗浓度的氨基糖苷类抗生素对培养的马 BM-MSCs 有毒性。透明质酸对培养 MSC 活力、增殖和介质分泌的影响最小。
根据这些发现,不建议在治疗前将氨基糖苷类抗生素与培养的马 BM-MSCs 混合。