- Strategy: WHO crash plan against snake bite mortality
Snake bites kill more than 100,000 people each year and cause triple amputations and permanent disabilities. According to the World Health Organization, the only effective treatment to nullify most of the toxic effects of a sting is high quality antidotes , but its mass production must overcome important obstacles. Some are technical, such as the complex - and dangerous - process of extracting the poison, in addition to the difficulty of studying and modifying the snake glands that control it. Other barriers are operational: it is a problem that fundamentally affects poor countries, which means that in many regions there is a lack of reliable data on the number and type of attacks, in addition to having poor distribution policies.
Now researchers from the Hubrecht Institute in Utrecht in the Netherlands have designed a method that can offer an alternative route. For the first time they have managed to grow organoids in the laboratory that recreate the venomous glands of snakes , miniaturized versions of organs produced in vitro from stem cells. In this case, these are small artificial glands that produce the active toxins found in snake venom. The results of his research have been published today in the scientific journal Cell .
Snakes and their venom have fed fears, myths and legends for millennia. But that is not their only relationship with society: their toxins are also an important source of drugs and are used to treat diseases at least from classical Greece. "Some drugs used today have been developed by isolating snake venom, for example to treat hypertension, " explains Yorick Post, one of the authors. "We hope that the organoids we have created serve to identify and validate possible new therapeutic agents and could open new strategies to the production of antidotes."
The project began when three PhD students were inspired by the advances that some of their colleagues were making in the cultivation of human organoids in the laboratory. "The first organoids were created from mice - the most common laboratory animal - but since then research has mainly focused on studying human tissues," Post says. "Our snake gland organoids are the first to be created from reptiles, which shows that we can recreate other animals, in addition to mammals ."
The researchers collaborated with snake experts from Leiden, Liverpool and Amsterdam to collect the venomous glands of nine different species , and then cultivated laboratory versions. Later they adjusted the conditions used in the cultivation of human organoids to adapt them to the ophidians; Since the body temperature of snakes is lower than that of mammals, their versions had to grow at lower temperatures (32º). " The similarity between the growth conditions of human tissues and that of snakes is amazing , the main difference in temperature," says another author, Jens Puschhof.
Through a high-resolution microscope, they observed that the resulting cells presented structures similar to those contained in venom in the snake glands. Further analysis confirmed that the organoids were also capable of producing the same components as the natural toxins produced by the snakes. That offers other researchers a unique possibility to study the production of toxins at the cellular level inside the gland. "We knew from other secretion systems, such as the pancreas and intestine, that specialized cells are produced by subsets of hormones," explains Joep Beumer. "Now we see for the first time that it is also the case of toxins produced by snake venom gland cells."
The researchers also discovered that, by modifying the factors in the growth medium of the organoids, they could also alter the composition of the poison , which allows them to control the type of toxin that is produced. This first crop of reptile organoids also suggests that the tissues of other vertebrate animals (such as lizards or fish) can also be generated with this system . So far, the authors are accumulating a large sample of venomous gland organoids from 50 poisonous animals to study the different types of toxin.
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