In Vitro Modeling of the Blood–Brain Barrier for the Study of Physiological Conditions and Alzheimer’s Disease

Abstract

The blood–brain barrier (BBB) is an essential structure for the maintenance of brain homeostasis. Alterations to the BBB are linked with a myriad of pathological conditions and play a significant role in the onset and evolution of neurodegenerative diseases, including Alzheimer’s disease. Thus, a deeper understanding of the BBB’s structure and function is mandatory for a better knowledge of neurodegenerative disorders and the development of effective therapies. Because studying the BBB in vivo imposes overwhelming difficulties, the in vitro approach remains the main possible way of research. With many in vitro BBB models having been developed over the last years, the main aim of this review is to systematically present the most relevant designs used in neurological research. In the first part of the article, the physiological and structural–functional parameters of the human BBB are detailed. Subsequently, available BBB models are presented in a comparative approach, highlighting their advantages and limitations. Finally, the new perspectives related to the study of Alzheimer’s disease with the help of novel devices that mimic the in vivo human BBB milieu gives the paper significant originality.

A human-derived neurovascular unit in vitro model to study the effects of cellular cross-talk and soluble factors on barrier integrity

“…Thus, the tri-culture best recapitulates the physiological and structural composition of the human NVU compared to the monoculture and co-culture layouts. Indeed, it has been previously reported that the crosstalk and exchange of growth factors between each cell type are enhanced and promoted in such multicellular microenvironment than in more simplified and reductionist single cell type models ( Schreiner et al, 2022 ). Following optimization of the cell culture media composition, cell density, and cell seeding strategies we established a 10-day cell culture protocol where each cell type of the model was seeded in the respective compartment at a specific time point of the study ( Figure 1C ).…”

Tumor Treating Fields (TTFields) Induce Cell Junction Alterations in a Human 3D In Vitro Model of the Blood-Brain Barrier

“…The most widely used in vitro model of the BBB is based on co-culture of the BBB component cells seeded on transwell inserts lodged onto well plates. This type of model replicates in vivo conditions more precisely compared to monocultures without requiring stringent handling methods [ 33 , 35 ]. The co-culture of endothelial cells with pericytes proved to be a stable and useful BBB model [ 36 , 37 , 38 ].…”

Intrathecal Pseudodelivery of Drugs in the Therapy of Neurodegenerative Diseases: Rationale, Basis and Potential Applications

“…Within neurons (green), proteins may also accumulate in intracellular aggregates, which are associated with the accumulation of glial cells and neuronal dysfunction. Modified from Schreiner et al [ 7 ] (Magda Pîrțac originally designed this figure by using Adobe Fresco).…”