The effects of therapeutic concentrations of gentamicin, amikacin and hyaluronic acid on cultured bone marrow-derived equine mesenchymal stem cells.
Abstract: 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.
© 2013 EVJ Ltd.
Publication Date: 2013-02-28 PubMed ID: 23448189DOI: 10.1111/evj.12045Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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The research investigates the effects of various substances on horse bone marrow stem cells in the lab, finding that certain antimicrobials are harmful to the cells while hyaluronic acid has minimal negative impact.
Study Purpose and Methodology
- The study aimed to determine the impacts of therapeutic doses of gentamicin, amikacin, and hyaluronic acid on horse bone marrow mesenchymal stem cells (BM-MSCs).
- Bone marrow-derived mesenchymal stem cells were extracted from four healthy, mature horses and cultivated separately.
- These cells were exposed to gentamicin, amikacin, hyaluronic acid, or a control of 1% penicillin/streptomycin under sterile conditions.
- Parameters such as cell viability, proliferation, the secretion of signaling compounds, and alterations in culture media pH were meticulously measured.
Study Findings
- Exposing the stem cells to gentamicin, an antimicrobial, resulted in more than 95% cell death after 45 minutes. Similary, more than 95% of cells died after two hours exposure to amikacin, another antimicrobial.
- However, when exposed to hyaluronic acid, an organic compound frequently found in the body, or the control substance (1% penicillin/streptomycin) for up to six hours, cell viability remained high. Specifically, 80% success was noted with hyaluronic acid and more than 93% with the control substance.
- All substances tested resulted in an initial drop in media pH but this was quickly leveled out and remained steady over the six-hour incubation period.
- There were no significant differences noted between the control substance and hyaluronic acid in terms of cell proliferation or the secretion of signaling compounds.
Conclusions Drawn from the Study
- Therapeutic doses of aminoglycoside antimicrobials like gentamicin and amikacin have been found to be toxic to cultured equine bone marrow mesenchymal stem cells.
- The effects of hyaluronic acid on the same kind of cells appear to be minimal, suggesting it may be a safer choice for co-injection.
- Based on these findings, the researchers recommend against combining aminoglycoside antimicrobials with bone marrow stem cells for therapeutic treatments in horses due to the toxic effect these drugs have on the cells.
Cite This Article
APA
Bohannon LK, Owens SD, Walker NJ, Carrade DD, Galuppo LD, Borjesson DL.
(2013).
The effects of therapeutic concentrations of gentamicin, amikacin and hyaluronic acid on cultured bone marrow-derived equine mesenchymal stem cells.
Equine Vet J, 45(6), 732-736.
https://doi.org/10.1111/evj.12045 Publication
Researcher Affiliations
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, USA.
MeSH Terms
- Amikacin / administration & dosage
- Amikacin / pharmacology
- Animals
- Anti-Bacterial Agents / administration & dosage
- Anti-Bacterial Agents / pharmacology
- Cell Culture Techniques
- Cell Proliferation
- Cell Survival / drug effects
- Cells, Cultured
- Dose-Response Relationship, Drug
- Gentamicins / administration & dosage
- Gentamicins / pharmacology
- Horses
- Hyaluronic Acid / administration & dosage
- Hyaluronic Acid / pharmacology
- Hydrogen-Ion Concentration
- Macrophages / drug effects
- Mesenchymal Stem Cells / drug effects
- Viscosupplements / administration & dosage
- Viscosupplements / pharmacology
Citations
This article has been cited 6 times.- Stancioiu F, Bogdan R, Bulumac B, Ivanescu B, Dumitrescu R. Decontamination of Two Umbilical Cord Blood Grafts Prior to Autologous Administration.. Maedica (Bucur) 2022 Dec;17(4):885-892.
- Madbouly N, Azmy A, Salama A, El-Amir A. The nephroprotective properties of taurine-amikacin treatment in rats are mediated through HSP25 and TLR-4 regulation.. J Antibiot (Tokyo) 2021 Sep;74(9):580-592.
- Pezzanite L, Chow L, Hendrickson D, Gustafson DL, Russell Moore A, Stoneback J, Griffenhagen GM, Piquini G, Phillips J, Lunghofer P, Dow S, Goodrich LR. Evaluation of Intra-Articular Amikacin Administration in an Equine Non-inflammatory Joint Model to Identify Effective Bactericidal Concentrations While Minimizing Cytotoxicity.. Front Vet Sci 2021;8:676774.
- Velloso Alvarez A, Boone LH, Braim AP, Taintor JS, Caldwell F, Wright JC, Wooldridge AA. A Survey of Clinical Usage of Non-steroidal Intra-Articular Therapeutics by Equine Practitioners.. Front Vet Sci 2020;7:579967.
- Pezzanite L, Chow L, Piquini G, Griffenhagen G, Ramirez D, Dow S, Goodrich L. Use of in vitro assays to identify antibiotics that are cytotoxic to normal equine chondrocytes and synovial cells.. Equine Vet J 2021 May;53(3):579-589.
- Bogers SH. Cell-Based Therapies for Joint Disease in Veterinary Medicine: What We Have Learned and What We Need to Know.. Front Vet Sci 2018;5:70.
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