Cytotoxicity of Local Anesthetics on Human Mesenchymal Stem Cells

Rahnama, Ruyan; Wang, Miqi; Dang, Alexis; Kim, Hubert T.; Kuo, Alfred C.

doi:10.2106/jbjs.k.01291

Cited by 57 publications

(61 citation statements)

References 2 publications

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“…1-3, 9-12 While the main therapeutic targets of LAs are voltage-gated sodium channels in neuronal cells, there is potential for them to have off-target effects on other cells in the microenvironment, including MSCs and macrophages. Several studies have demonstrated anti-inflammatory effects to LAs.…”

Section: Introductionmentioning

confidence: 99%

The effect of local anesthetic on pro-inflammatory macrophage modulation by mesenchymal stromal cells

Gray

Marrero-Berríos

Weinberg

et al. 2016

International Immunopharmacology

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Administering local anesthetics (LAs) peri- and post-operatively aims to prevent or mitigate pain in surgical procedures and after tissue injury in cases of osteoarthritis (OA) and other degenerative diseases. Innovative tissue protective and reparative therapeutic interventions such as mesenchymal stromal cells (MSCs) are likely to be exposed to co-administered drugs such as LAs. Therefore, it is important to determine how this exposure affects the therapeutic functions of MSCs and other cells in their target microenvironment. In these studies, we measured the effect of LAs, lidocaine and bupivacaine, on macrophage viability and pro-inflammatory secretion. We also examined their effect on modulation of the macrophage pro-inflammatory phenotype in an in vitro co-culture system with MSCs, by quantifying macrophage tumor necrosis factor (TNF)-α secretion and MSC prostaglandin E2 (PGE2) production. Our studies indicate that both LAs directly attenuated macrophage TNF-α secretion, without significantly affecting viability, in a concentration- and potency-dependent manner. LA-mediated attenuation of macrophage TNF-α was sustained in co-culture with MSCs, but MSCs did not further enhance this anti-inflammatory effect. Concentration- and potency-dependent reductions in macrophage TNF-α were concurrent with decreased PGE2 levels in the co-cultures further indicating MSC-independent macrophage attenuation. MSC functional recovery from LA exposure was assessed by pre-treating MSCs with LAs prior to co-culture with macrophages. Both MSC attenuation of TNF-α and PGE2 secretion were impaired by pre-exposure to the more potent bupivacaine and high dose of lidocaine in a concentration-dependent manner. Therefore, LAs can affect anti-inflammatory function by both directly attenuating macrophage inflammation and MSC secretion and possibly by altering the local microenvironment which can secondarily reduce MSC function. Furthermore, the LA effect on MSC function may persist even after LA removal.

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Section: Introductionmentioning

confidence: 99%

The effect of local anesthetic on pro-inflammatory macrophage modulation by mesenchymal stromal cells

Gray

Marrero-Berríos

Weinberg

et al. 2016

International Immunopharmacology

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“…Ropivacaine and bupivacaine had limited toxicity in human mesenchymal stem cells, but lidocaine has shown to reduce mesenchymal stem cell viability. 7 Finally, the association of HA with local anesthetics reduced their cytotoxicity with bupivacaine but not lidocaine, suggesting different mechanisms of injury between the two compounds. 8 Esterification of steroids, producing crystals of various sizes, is another structural option that makes them water insoluble, slowly degraded by the synovial esterase enzymes, with a delayed absorption and a more prolonged local antiinflammatory effect.…”

Section: Resultsmentioning

confidence: 98%

Synoviology: a new chapter entitled to joints care

et al. 2017

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A B S T R A C T REVIEW ARTICLE ASIAN JOURNAL OF MEDICAL SCIENCESIn order to extensively investigate on the synovial membrane -related diseases, we outlined a specific medical branch named "Synoviology", targeted to the physiopathology and therapy of synovial membrane dysfunction. We searched Pubmed/Medline using the terms "synovial disease", "therapy", "synovial membrane", "joints" and "drugs", alone and combined. Selected papers from 1960 to 2015 were chosen based on their content (evidence-based quality and reliability). Clinical and experimental articles were included. Viscosupplementation with structurally different hyaluronic acid compounds, for restoration of the synovial membrane, and cartilage. The impact of other old and new medical treatments either locally or systemically administered was also included. Synoviology integrates biological, clinical and biochemical information for the progress of new therapeutic options in osteo-articular pathology.

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“…21 In a similar study, when MSCs were exposed to bupivacaine, ropivacaine, or lidocaine, administration of lidocaine was found to have a significant cytotoxic effect. 22 Moreover, when MSC monolayers were exposed directly to bupivacaine, ropivacaine, and mepivacaine, all three showed time-and concentration-dependent cytotoxic effects. 23 Based on this in vitro work, it is clear that local anesthetics may have a deleterious effect on the function of MSCs.…”

Section: Potential Implications Of Anesthetics On Mscsmentioning

confidence: 97%

“…21 Dans une étude semblable, lorsque des CSM ont été exposées à la bupivacaïne, à la ropivacaïne ou à la lidocaïne, on a observé que l'administration de lidocaïne avait un effet cytotoxique significatif. 22 En outre, lorsque des monocouches de CSM ont été exposées directement à de la bupivacaïne, de la ropivacaïne ou de la mépivacaïne, ces trois agents ont tous démontré des effets cytotoxiques dépendants de la durée et de la concentration. 23 Sur la base de ces travaux in vitro, il est clair que les anesthésiques locaux pourraient avoir un effet délétère sur la fonction des CSM.…”

Section: Les Voies De Transmission Thérapeutiques Des Csmunclassified