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.

The FDA is Responsible for the Drug Shortages


The Food and Drug Administration (FDA) has implemented extremely restrictive drug policies that are generating drug shortages across the nation. According to the Regenexx blog, clinicians all over the United States have been feeling the effects of this pinch for some time.

Centeno gives the following example: “we were paying about $1 a bottle for local anesthetic, now when we can find it-that same bottle is often $4 a bottle.” As you might guess, this is having a significant effect on patient care, since surgery centers cannot get their hands on certain drugs. Cancer patients have been dramatically affected, since stocks of cheap, generic drugs are drying up.

On his blog, Centeno predicted that these shortages were due to “an ascendant hyper-regulatory FDA.” As it turns out, Centeno’s instincts were dead on. A Congressional hearing has confirmed that the FDA is responsible for the drug shortages. The “new FDA” focuses on reducing the so-called “type 1 regulatory” errors. Type 1 regulatory errors occur if a dangerous drug is allowed to go through market. It is certainly a proper function of the FDA to prevent type 1 regulatory errors. However, by overly focusing on type 1 regulatory errors, the agency is guilty of type 2 errors, in which good drugs are from the market.

The number of people harmed by type 2 errors is very large indeed. One estimate puts the number at 82,000 lives a year. Forbes Magazine documented the enormous rise in Warning Letters issued by the FDA. These Warning Letters have essentially shut down the production of generic drugs. These factories were shut down not because there was an actual problem, but because of theoretical risks due to current Good Manufacturing Practice violations.

The FDA employees that issued the letters did not take into account the consequences of their actions; namely that entire factories would have to shut down. A fair number of these manufacturers may or may not be able to reopen their production lines for these cheap medications because of the increased regulatory costs. Some of these companies may even have had to build new facilities. Many companies will simply drop the production line and this means less generic drugs. Also for many of these drugs, there are no brand name alternatives anymore, and the consequences of all this is that our hyper-regulatory FDA that has chosen to focus on reducing one type of regulatory error and by being only focused in one direction, they place the public’s health at risk.

What is the solution? We need a FDA that is as concerned with type 1 errors as they are with type 2 errors. This will balance these concerns so that the public is as protected from bad drugs as much as it’s protected from delays in promising therapies or shortages of generic drugs.