Reducing animal testing with stem cells and electronic petri dishes

botoxThough the celebrities at Sunday’s Academy Awards worked hard to sport unique clothing and hair styles, I bet many had something in common: Botox injections. Botox, an FDA-approved, marketed form of Botulism neurotoxin, is well known for its wrinkle reducing effects. The neurotoxin’s other claim to fame is the fact that it’s the most lethal, naturally occurring poison known. Inhaling a minuscule amount – just 0.0000007 grams! – is enough to kill a 150 pound person.

Much smaller, non-lethal doses of Botulism neurotoxin are obviously used for its cosmetic application. It’s also used to treat a wide range of disorders including back pain, migraines and muscle spasms related to stroke and cerebral palsy. Because the toxin is produced naturally by the Clostridium botulinum bacteria, the amount of toxin can vary in each batch during the manufacturing process. So, it’s critical to carefully analyze the Botulism neurotoxin dose.  The standard test which has been around since the 1920’s is the mouse bioassay. During the test, increasing concentrations of the neurotoxin are injected into mice which are then observed for signs of paralysis (Botulism neurotoxin acts by blocking communication between nerves and muscle).

As you might expect, the lab mice suffer during the test, sometimes suffocating during the process. Because of the large market for these Botulism neurotoxin-based products, it’s estimated that about 600,000 laboratory mice in US and Europe are killed via the mouse bioassay each year. Though the media often portrays scientists as callous, cold-hearted people that couldn’t care less about the welfare of their lab animals, in reality, it’s just the opposite. Case in point: a research group at the University of Bern in Switzerland reported this week in Frontiers in Pharmacology that they have devised an alternative system that could help make this mouse bioassay obsolete.

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Multi-electrode assay petri dish. Credit: Multichannel Systems

To set up this new assay system, the researchers relied on mouse embryonic stem cells. The researchers added chemicals to the cells, stimulating them to transform into nerve cells, or neurons. These stem cell-derived neurons were placed in specialized petri dishes that look something like a computer chip. Wired with mini electrodes, the lab dishes allowed the continuous recording of electrical signals generated by the neurons. Adding small doses of Botox to the cells, the scientists could detect a shutdown of the neuron signaling which is the same underlying effect that causes paralysis in the mouse bioassay.

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Stem cell-derived neurons (green) grown on electrodes (outlined in white) allows monitoring of electrical nerve signals. Credit: Stephen Jenkinson, Institute for Infectious Diseases, University of Bern

This sensitive test could have applications beyond the detection of Botulism neurotoxin. The electrode dishes are easy to scale up and do not require highly trained staff. So, without the need for expensive animal testing, this system could be used as a high throughput drug screening platform to find other substances that have beneficial effects on neuron signaling.

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