Neural spheres on nylon
Scientists Accidentally Created Brain Organoids on Scaffolds for Drug Screening
Natalia Bykova, ITEB RAS Press Service
Frameworks made of ultrathin nylon fibers allow you to simulate the brain's work taking into account the interaction of neurons with the extracellular matrix. The results are published in the journal ACS Chemical Neuroscience (Antonova et al., Rapid Generation of Neurospheres from Hippocampal Neurons Using Extracellular-Matrix-Mimetic Scaffolds).
The creation of three–dimensional organoids - tissues grown in a test tube, very close in structure to individual parts of real organs - is a relatively new direction in science. The first organoids, which were a miniature likeness of the human brain, were obtained in Austria in 2013. In subsequent years, this area developed quite rapidly: organoids of the kidneys, liver, lungs, and retina were presented. These protostructures are considered a promising tool for biological and medical research. But the methods of their creation are not yet perfect. In particular, the cultivation of 3D brain organoids from human stem cells has a significant drawback: it does not take into account the influence of the extracellular matrix of the environment (ECM), which plays a key role not only during development, but also in the physiological and pathological conditions of the adult brain.
Scientists from the Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences have proposed a new method for obtaining a "mini-brain". It consists in creating neurospheres on ultrathin nylon nanofibers close in size to the structures of the extracellular matrix of the brain. The idea of developing such a technology was born by chance, during another study – the growth of rat hippocampal neurons on scaffolds made of ultrathin nanofibers.
"Initially, we investigated the effects of the nanotopology of the material on the growth of neuronal processes in order to obtain material for accelerated regeneration of damaged nerves," says Olga Antonova, one of the authors of the work, a researcher at ITEB RAS. – It has been observed that with a sufficiently low cell density, organoids begin to form. They are usually obtained at a higher density. This observation grew into a separate study. It turned out that the growth of neurospheres is stimulated by our scaffolds – similar in size to the structures of the VCM, they accelerate cell migration and provide a favorable environment for the survival of astrocytes in the neurosphere. Later, we found out the role of the integrin family adhesion receptors in the process of neuronal migration on the substrate and the formation of neurospheres and proved that the resulting neurospheres have greater functional activity compared to single cells grown in 2D culture, that is, they best mimic living nerve tissue."
The main advantage of the new method is the possibility of studying extracellular interactions (cell – matrix). In addition, the authors note, the use of a new approach allows you to optimize the research process. Firstly, it is more economical, about 1.5-2 times, to spend biomaterial cells to obtain neurospheres. Secondly, it was fast enough to create organoids in just 1 day, whereas researchers who previously received "floating", non-attached neurospheres from hippocampal neurons, this process took 6-7 days. The proposed method also makes it possible to conduct microscopic and electrophysiological studies more efficiently, since the neurospheres are attached to the substrate.
According to scientists, the created 3D organoids can be used for drug screening, modeling of brain development processes and research of neurodegenerative diseases (Alzheimer's and Parkinson's disease). Further work of the group will be related to a detailed study of the mechanisms of interaction of neurons with ultrathin fibers that mimic the extracellular matrix.
The work was supported by the RPF grant No. 19-74-10097
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