Poisonous snakes kill more than 90,000 people each year across the globe, with about 1.2 million to 5.5 million snake bites occur annually. Despite the venomous bite, scientists have limited knowledge of the snake’s venom, complicating efforts to develop treatments. A new study has found that snake venom gland cells can be cultured in the lab as adult-stem-cell-based organoids, producing real venom, which can be used to develop treatments.
The inland taipan (Oxyuranus microlepidotus), also commonly known as the western taipan, the small-scaled snake or the fierce snake is the by far the most toxic of any snake – much more so than even that of sea snakes – and it has the most toxic venom of any reptile when tested on human heart cell culture. It is estimated that one bite possesses enough lethality to kill at least 100 fully grown men. Source: https://en.wikipedia.org/wiki/Inland_taipan
A team of researchers at the Hans Clevers at the Hubrecht Institute (KNAW) has developed a way to grow snake venom gland cells as organoids, which secrete active toxins found in snake venom. The new discovery holds promise to help reduce the impact of snake venom.
For years, scientists have created mini-organs or organoids for adult human and mouse stem cells, which are able to divide and grow into new types of tissues in the body. They have been used to create tiny guts, brains, and livers, for study and possible development of treatments. However, they haven’t used the method in reptiles before.
Organoids have become a crucial tool for scientists to study many disease processes, and even in testing potential drugs. Now, they are being used in the production of snake venom, as published in the study published in the journal Cell.
“More than 100,000 people die from snake bites every year, mostly in developing countries. Yet the methods for manufacturing antivenom haven't changed since the 19th century. It's clear there is a huge unmet medical need for new treatments,” Hans Clevers of the Hubrecht Institute for Developmental Biology and Stem Cell Research at Utrecht University in the Netherlands, said in a statement.
Collect venom glands from snakes
The team wanted to see if they can produce or grow mini versions of reptile organs in the laboratory, starting off with snakes. They set up a team-up with snake experts in Leiden, Amsterdam, and Liverpool, collecting venom glands from nine different snakes.
They tried to grow mini versions of the glands in a dish. With the use of some changes in the environment, the team developed a special method that helps grow snake venom glands. One of the main differences in growing mini organs from humans is that snakes have lower body temperature, which meant that the snake organoids only grew in temperatures lower than 32 ºC.
The vast majority of venom toxins
The team used a high-resolution microscope to study the organoids produced. They found that in the organoids, there are many venom components or toxins made by the snakes.
"We know from other secretory systems such as the pancreas and intestine that specialized cell types make subsets of hormones. Now we saw for the first time that this is also the case for the toxins produced by snake venom gland cells", Joep Beumer from the Hubrecht Institute, explained.
Further, the team discovered that tweaking certain factors in the growth of organoids can help change the contents of the venom, providing control on which type of venom will be produced.
Aside from being able to determine venom content, the new study can help scientists produce venom to be used for antivenom production. It can also be utilized to produce targeted venom-based drugs in the future.
“Future studies may use venom gland organoids to dissect the stimuli and timing of venom production and secretion. The ability to indefinitely expand these organoids and repeatedly harvest venom supernatants in a highly defined environment may help overcome hurdles posed by the significant variation in snake venom composition, the researchers wrote in the paper.
“Finally, the current study opens new avenues for bioprospecting of snake venom components and may be developed into a production platform for (modified) snake venom, allowing novel therapeutic strategies to tackle snakebite,” they added.
Post, Y., Pushchhof, J., Buemer, J., Richardson. M., Casewell, N., Clevers, H. et. al. (2020). Snake Venom Gland Organoids. Cell. https://www.cell.com/cell/fulltext/S0092-8674(19)31323-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867419313236%3Fshowall%3Dtrue