The buzzword "organoids"
Organs from a test tube
Finding the optimal anti–cancer therapy for a particular patient, studying the Neanderthal brain structure, obtaining snake venom without contact with a dangerous reptile - what do these scientific studies have in common? All of them are carried out on organoids – obtained "in vitro" likenesses of real organs. Organoids are a new word in cell biology and biomedicine of the new century. What are they, how are they obtained and what are they used for?
Like everything else in our world, cellular and molecular biology are also subject to "fashion trends". A few years ago, apoptosis was the buzzword. Then it became fashionable to work with the CRISPR/Cas genome editing method and talk about exosomes – membrane bubbles with which cells "communicate" with each other. Another of the modern "fashionable" trends is the creation of so–called organoids.
Organoids are three–dimensional cellular structures grown "in vitro". Their creation is based on the principle of "self-assembly" of a group of stem cells or even already differentiated cells. Now researchers most often use induced pluripotent stem cells, which are obtained from ordinary cells of the body, returning them "to childhood" by genetic reprogramming. If at the beginning of differentiation it is possible to give such cells a push in the right direction by influencing them with a certain combination of biologically active molecules, then interaction processes begin between them. The cell mass conditionally determines "where its head is and where its tail is", and begins to reproduce the embryonic development program.
Of course, the development processes in the body are under strict versatile control, and the genetic "program" is not fully deciphered, so the result is not quite a full-fledged organ. However, this structure turns out to be similar to it in molecular and histological characteristics and is capable of performing some part of the physiological function of a full-fledged organ.
To date, it has already been possible to create miniature primitive analogues of the brain, intestines, liver, kidney, pancreas, prostate, lung, stomach, breast, eyes, etc. With their help, researchers gain not only fundamental knowledge about the processes of embryonic development. Organoids are also used as convenient models for studying the key moments of the occurrence of a particular pathology, as well as searching and testing ways to treat and prevent it.
An organoid of the eye differentiated from induced pluripotent stem cells. Phase contrast. Photo member-correspondent. RAS M.A. Lagarkova (Moscow).
For example, Dutch scientists have grown an intestinal organoid containing different types of epithelial cells from a single stem cell to understand how the infamous bacterium Helicobacter pylori interacts with intestinal tissues (this process is difficult to study even on a model animal). By the way, even a dense cancerous tumor is not a simple cluster of cells – it is usually structured. And organoids obtained on the basis of modern technology of growing three-dimensional cellular structures can be used in personalized medicine for the selection of effective anti-cancer treatment.
With the help of new cellular technologies and advances in paleogenetics, it has become possible to learn even some features of the Neanderthal brain! By replacing one gene in the progenitor cells of the human brain organoid, which plays an important role in the early development of the brain, with its Neanderthal "copy", scientists were able to see a picture similar to that observed in the brains of autistic children.
Work on the creation of human and other mammalian organoids has been successfully carried out for a number of years – back in 2013, they were included in the top ten outstanding discoveries according to the journal Science. And recently, scientists from the Netherlands and Great Britain have created the first organoids of cold–blooded animals - snakes from the families of asps (it includes cobras) and vipers.
The aim of the work is to develop a method for obtaining snake venom necessary for the manufacture of antidotes, as well as some therapeutic drugs, avoiding contact with these dangerous animals. Nowadays, with the help of animal and human cells grown in industrial bioreactors, the most important medical preparations are produced, such as insulin, interferon, blood clotting factor, enzymes, etc. But it was impossible to use such an approach in the case of snakes: their poisonous glands produce complex mixtures of different toxins containing from tens to hundreds of components. And different specialized cells can synthesize them, whereas ordinary cell cultures consist of only one type of cell.
The researchers removed stem, undifferentiated cells from the venom glands of nine species of snakes, from which they managed to grow miniature replicas of venom glands. These organoids really contained tissues with different types of cells specializing in the production of different toxins, so that "at the exit" scientists received a real snake venom.
There are many more points of practical applications of such "organoid" technologies. And the most exciting of them lies in the mainstream of regenerative medicine: researchers hope to eventually learn how to grow organs for transplantation using their own cells of the corresponding human organ.
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