A Comprehensive Review on Utilizing Human Brain Organoids to Study Neuroinflammation in Neurological Disorders

Abstract

Most current information about neurological disorders and diseases is derived from direct patient and animal studies. However, patient studies in many cases do not allow replication of the early stages of the disease and, therefore, offer limited opportunities to understand disease progression. On the other hand, although the use of animal models allows us to study the mechanisms of the disease, they present significant limitations in developing drugs for humans. Recently, 3D-cultured in vitro models derived from human pluripotent stem cells have surfaced as a promising system. They offer the potential to connect findings from patient studies with those from animal models. In this comprehensive review, we discuss their application in modeling neurodevelopmental conditions such as Down Syndrome or Autism, neurodegenerative diseases such as Alzheimer's or Parkinson's, and viral diseases like Zika virus or HIV. Furthermore, we will discuss the different models used to study prenatal exposure to drugs of abuse, as well as the limitations and challenges that must be met to transform the landscape of research on human brain disorders.

Keywords: Cell culture; Drugs of abuse; Human brain organoids; Neurodevelopment; Stem cells.

Fig. 1

Different types of microglia can be incorporated into brain organoids, which can serve as valuable model systems. Sources of such microglia include (1) immortalized microglial cell lines, (2) primary microglia from patient brain samples, (3) microglia derived from hiPSCs, and (4) microglia derived from PBMCs isolated from patient blood samples