Glia-neuron interactions in neurological diseases: Testing non-cell autonomy in a dish

Abstract

For the past century, research on neurological disorders has largely focused on the most prominently affected cell types - the neurons. However, with increasing knowledge of the diverse physiological functions of glial cells, their impact on these diseases has become more evident. Thus, many conditions appear to have more complex origins than initially thought. Since neurological pathologies are often sporadic with unknown etiology, animal models are difficult to create and might only reflect a small portion of patients in which a mutation in a gene has been identified. Therefore, reliable in vitro systems to studying these disorders are urgently needed. They might be a pre-requisite for improving our understanding of the disease mechanisms as well as for the development of potential new therapies. In this review, we will briefly summarize the function of different glial cell types in the healthy central nervous system (CNS) and outline their implication in the development or progression of neurological conditions. We will then describe different types of culture systems to model non-cell autonomous interactions in vitro and evaluate advantages and disadvantages. This article is part of a Special Issue entitled SI: Exploiting human neurons.

Keywords: Direct conversion; In vitro systems; Induced pluripotent stem cells; Neurodegeneration; Non-cell autonomy.

Figure 1. Scheme of different co-culture settings used to model non-cell autonomous aspects of neurological disorders

Left panel: different cell types can be combined in classic co-cultures with direct contact or in sandwich co-cultures with one cell type on a glass coverslip facing upside down. Alternatively, cells can be seeded in transwells or inserts without direct contact sharing only the secreted factors in the medium. Right panel: Microfluidic chambers can be used to model various aspects of neurological disorders such as axonal growth, myelination, innervation or BBB permeability. Bottom: two systems can be kept in parallel and medium only can be transferred in between with the option of replenishing nutrients or growth factors to avoid starvation. See table 2 for applications and exemplary references for the use of each system.