The current model of brain tissue
Bioengineers from Tufts University, working under the guidance of Professor David Kaplan, have created a three-dimensional model, similar in structure and function to the tissue of the rat cerebral cortex. In laboratory conditions, it can remain viable for more than two months.
Currently, two-dimensional cell cultures are used to study the behavior of neurons under controlled conditions. However, this approach does not allow reproducing the complex structure of the brain, consisting of isolated regions of white and gray matter. Gray matter mainly consists of neuronal bodies, whereas white matter consists of axon bundles, long processes with which neurons exchange electrical impulses. Brain injuries and diseases often affect these regions in different ways, so models for studying these processes must adequately reproduce the structure of brain tissue.
Earlier attempts to grow three-dimensional neural structures in a gel-like environment were unsuccessful. Such models died quickly and did not allow reproducing the functions of the nervous tissue. It turned out that giving neurons the opportunity to grow in a three-dimensional matrix is not enough to create a full-fledged model of brain tissue, the extracellular matrix of which has a complex structure in which local signals form zones favorable for the growth and functioning of different cells.
The authors solved this problem with the help of a new composite biomaterial consisting of two components with different physical properties: a spongy framework made of silk protein and a softer collagen gel. The framework allows neurons to gain a foothold, and the gel provides the possibility of axon growth.
Neurons form functional networks inside the pores of the skeleton (dark zones).
To obtain a two-phase model (gray and white matter), the researchers gave the spongy skeleton the shape of a bagel and populated it with rat neurons. A collagen gel was inserted into the middle of the structure, which subsequently filled the voids of the spongy frame. Within a few days, the neurons formed functional structures inside the pores of the skeleton, and their axons sprouted into the depth of the gel-filled core and formed synapses with the axons of neurons on the opposite side of the "bagel". As a result, a zone of white matter surrounded by a zone of gray matter formed in the core of the frame.
A diagram of the model demonstrating the compartmentalization of gray and white matter.
Neurons of rats are attached to the framework ("bagel"),
and their axons penetrate into the gel-filled center
(marked with green fluorescent dye).
Over the next few weeks, the researchers conducted a series of experiments, the results of which showed that, compared with two-dimensional models, cells cultured on a new scaffold have a higher expression of genes involved in the growth and functioning of neurons. They also demonstrate stable metabolic activity for 5 weeks, whereas when neurons are grown in a gel matrix, this indicator begins to deteriorate within the first 24 hours. The neurons of the new model are also characterized by levels of electrical activity and susceptibility to electrical signals similar to those demonstrated by intact brain cells.
To simulate traumatic brain injury, a heavy object was dropped onto the model from different heights. The changes in the electrical and chemical activity of neurons recorded after this corresponded to the changes observed in the corresponding animal models.
An image of a porous silk protein frame obtained using an electron microscope.
Currently, the authors are working on improving their model. They have already demonstrated the possibility of creating a framework consisting of six concentric rings, each of which can be populated with different types of neurons. This will reproduce the six layers of the human cerebral cortex.
The researchers believe that their proposed model is optimal for studying both the normal functioning of brain tissue and the processes occurring in it in various diseases and traumatic injuries. And the results obtained with its use will help in the development of new methods of treating brain disorders.
Article by Min D. Tang-Schomer et al. Bioengineered functional brain-like cortical tissue is published in the journal Proceedings of the National Academy of Sciences.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the National Institute
of Biomedical Imaging and Bioengineering: Bioengineers Create Functional 3D Brain-like Tissue.
19.08.2014