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Review
. 2024 Mar 20:15:20417314241235527.
doi: 10.1177/20417314241235527. eCollection 2024 Jan-Dec.

Current progress and challenges in the development of brain tissue models: How to grow up the changeable brain in vitro?

Alla B Salmina  1   2 , Olga P Alexandrova  1   2 , Anton S Averchuk  1   2 , Sofia A Korsakova  2 , Mikis R Saridis  2 , Sergey N Illarioshkin  1 , Stanislav O Yurchenko  2
Affiliations
Review

Current progress and challenges in the development of brain tissue models: How to grow up the changeable brain in vitro?

Alla B Salmina et al. J Tissue Eng. .

Abstract

In vitro modeling of brain tissue is a promising but not yet resolved problem in modern neurobiology and neuropharmacology. Complexity of the brain structure and diversity of cell-to-cell communication in (patho)physiological conditions make this task almost unachievable. However, establishment of novel in vitro brain models would ultimately lead to better understanding of development-associated or experience-driven brain plasticity, designing efficient approaches to restore aberrant brain functioning. The main goal of this review is to summarize the available data on methodological approaches that are currently in use, and to identify the most prospective trends in development of neurovascular unit, blood-brain barrier, blood-cerebrospinal fluid barrier, and neurogenic niche in vitro models. The manuscript focuses on the regulation of adult neurogenesis, cerebral microcirculation and fluids dynamics that should be reproduced in the in vitro 4D models to mimic brain development and its alterations in brain pathology. We discuss approaches that are critical for studying brain plasticity, deciphering the individual person-specific trajectory of brain development and aging, and testing new drug candidates in the in vitro models.

Keywords: Brain plasticity; bioengineering; blood-brain barrier; blood-cerebrospinal fluid barrier; neurogenic niche; neurovascular unit.

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Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Principles of structural and functional organization of BBB and BCSFB. Blood-CSF barrier, consisting of choroid plexus (CP) endothelial cells (ECs) and choroid plexus epithelial cells (CPECs), ensures its barrier function by tightly coupled CPECs, whereas ECs are highly fenestrated. In contrast, integrity of the blood-brain barrier is determined by endothelium where brain microvessel endothelial cells (BMECs) are contacted via tight junctions. The ventricular barrier (VB), located right between BBB and BCSFB, has low integrity since ependymal cells (EpCs) are mainly coupled via gap junctions and have high paracellular permeability.
Figure 2.
Figure 2.
Brain plasticity in the SVZ. Plasticity of neurogenic niche consisting of ventricular barrier ependymal cells (EpCs), neural stem cells (NCSs), transitory amplifying cells, neuronal progenitor cells (NPCs), neuroblasts, immature neurons, astrocytes, extracellular matrix proteins and other components, is under the control of blood-brain barrier (BBB) and blood-CSF barrier (BCSFB) integrity. Appropriate stimuli coming either from the blood in a case of BBB disruption or from the CSF due to choroid plexus (CP) activity induce two key long-term mechanisms of brain plasticity: angiogenesis and neurogenesis.
Figure 3.
Figure 3.
Timeline of technology evolution. The indications of the most typical in vitro BBB and BCSFB models and their main parameters are given on the chronological axis.–,,,,,,,,,, FSS: flow shear stress; TEER: transendo(epi)thelial electrical resistance; PET: polyethylene terephthalate. *TEER values are not normalized properly in the original model description.
Figure 4.
Figure 4.
Technological leaps in BBB, BCSFB and NN modeling. Transwell inserts, hollow fiber bioreactors and microfluidic chips as available tools to recreate brain tissue in vitro.
Figure 5.
Figure 5.
Summary of brain tissue models. The following parameters should be taken in consideration for reproducing the changeable brain in vitro: tissue composition, ECM mimicking, compartmentalization, tissue architecture, key brain plasticity parameters and monitoring techniques.
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