Snake Venom Gland Organoids
Unlocking possibilities for more effective production of bioactive compounds from snake venom
Leiden, January 23, 2020– The Hubrecht institute and MIMETAS investigated if venom molecules produced by snake venom gland organoids also function as actual venom using the OrganoPlate® platform.
Although snake bites are not very common in developed countries, snakebite envenoming is still estimated to be responsible for more than 100,000 deaths worldwide each year. The composition of snake venom differs greatly between snake species, requiring treatment with different antidotes for bites from different snakes. Treatment of snake envenoming is further complicated by logistical difficulties. Antidote production is expensive, labor intensive and not animal friendly as it requires keeping and milking of snakes, immunization of other animals, and collection and purification of the produced antibodies.
Researchers at Hubrecht institute have developed a method that may circumvent many of the issues encountered with the current snake venom treatments. Researchers in the lab of Hans Clevers isolated stem cells from the venom gland of the venomous cape coral snake. From these venom gland stem cells, they grew organoids: three-dimensional cell structures that show similarities to the actual venom gland of the cape coral snake. Using various techniques, the work published in Cell shows that the snake venom gland organoids produce many of the same molecules found in the venom of adult cape coral snakes.
The Hubrecht institute teamed up with MIMETAS to assess whether the venom molecules produced by the snake venom gland organoids also function as actual venom. MIMETAS used its OrganoPlate® platform to culture muscle fibers that express the nicotinic acetylcholine receptor. The team at MIMETAS showed that muscle fibers that were exposed to the venom molecules from the organoids were no longer able to respond to a molecule resembling acetylcholine. This indicates that the venom molecules from the organoids are likely binding to the acetylcholine receptor the same way that toxins from adult snakes do. The study published in Cell is the first to apply organoid technology to non-vertebrate species and opens up possibilities for easier, cheaper, and more animal friendly production of snake venom antidotes and other bioactive compounds present in snake venom.
Figure 1: C2C12 muscle cell cultures in OrganoPlate 2-lane stained for muscle marker Desmin (red), the acetylcholine receptor (green), and nuclei (Hoechst, blue).
Video 1: C2C12 muscle cells that weren't exposed to supernatant from the snake venom organoids show calcium wave propagation in response to acetyl choline receptor agonist carbachol (the movement of the green signal).
Video 2: Cells that were exposed to snake venom organoid supernatant don't respond to carbachol (no wave propagation observed)