Local Anesthesia Inhibits Mesenchymal Stem Cells


Anyone who has had dental work or particular out-patient procedures has had local anesthesia. Local anesthesia inhibits local sensory nerve function and induces numbness. Several studies have shown that when used at high concentrations, local anesthesia can cause particular cells to die. Therefore, some physicians worry that local anesthesia might affect stem cells, but the effects of local anesthesia on mesenchymal stem cells is largely unknown.

To this end, Michael Zaugg from the University of Alberta and his talented co-workers examined the effects of local anesthesia on mesenchymal stem cells from bone marrow. Their results were from experiments on cultured mesenchymal stem cells.

When mouse bone marrow mesenchymal stem cells were isolated and grown in culture and exposed to 100 micromolar concentrations of three different local anesthetics, lidcocaine, ropivacaine, and bupivacaine, they discovered that the mesenchymal stem cells grew much more slowly. In fact, the stem cells seemed to divide and then give up the ghost. Therefore, local anesthetics seemed to inhibit mesenchymal stem cell proliferation.

Upon further investigation, the stem cells stopped dividing at the point when they were supposed to start making new DNA. This phase of the life of the cell is called the S phase for synthesis phase, and the molecule made by the cell at this time is DNA. However, the mesenchymal stem cells exposed to local anesthetics failed to initiate DNA synthesis.

The next question Zaugg and his team asked was whether or not the stem cells had trouble making energy, which is a common feature of cell exposed to too much local anesthetic. Indeed, the mesenchymal stem cells exposed to local anesthetics showed reduced energy production.

A more sophisticated analysis called “microarray analysis,” which examines the gene expression patterns in a cell by a gene-by-gene basis, showed that those genes necessary for cell membrane synthesis were greatly decreased when the cells were exposed to local anesthetics. Furthermore, the mesenchymal stem cells exposed to local anesthetics differentiated quite poorly, and the microarray analysis confirmed this observation, since those genes necessary for differentiation in mesenchymal stem cells were down regulated in the presence of local anesthetics.

Before conclusions can be drawn about what local anesthetics do to a living creature during wound healing, more work must be done, First of all, these results from cultured cells may not hold true in a living organism. Also, the concentration of anesthetic used in this study is well above what are acknowledged to be toxic levels for these drugs. Therefore, while these results are informative and interesting, the must be interpreted with some caution.

Published by

mburatov

Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).

4 thoughts on “Local Anesthesia Inhibits Mesenchymal Stem Cells”

    1. I can try. Because this study was in vitro, which simply means that it was in a culture dish and not in a living critter, the concentrations are difficult to translate.

      Nevertheless, the molecular weight of lidocaine is 234.34, which means that in this study, the cells were exposed to 0.023 grams or 23 milligrams of lidocaine per liter of water. How do we translate that into something clinically relevant? The maximum adult lidocaine dosage for anesthesia is 4.5 mg/kg/dose that is not to be repeated within 2 hours. If you figure that your patient weighs 70 kg (just to pick a number), then that works out to 315 mgs of lidocaine per dose.

      What is the concentration in the body? Lidocaine has a volume of distribution of about 1 liter per kilogram body weight. Therefore, 315 mgs in 70 liters gives us a concentration of 4.5 mgs / liter. This is over five times less than the concentration used in this paper. Therefore, I would like to see a follow-up study that examines the effects of local anesthetics at clinically relevant concentrations and a demonstration that the use of local anesthetics actually slows healing. This paper, in my view, is just a start to understanding the effects of local anesthetics on mesenchymal stem cells.

      I hope this helps.
      MB

      1. Thanks. I was able to follow this but would probably not have been able to work it out witth confidence.

        Kevin

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