Studying Human Neurological Disorders Using Induced Pluripotent Stem Cells: From 2D Monolayer to 3D Organoid and Blood Brain Barrier Models

Abstract

Neurological disorders have emerged as a predominant healthcare concern in recent years due to their severe consequences on quality of life and prevalence throughout the world. Understanding the underlying mechanisms of these diseases and the interactions between different brain cell types is essential for the development of new therapeutics. Induced pluripotent stem cells (iPSCs) are invaluable tools for neurological disease modeling, as they have unlimited self-renewal and differentiation capacity. Mounting evidence shows: 1) various brain cells can be generated from iPSCs in 2-dimensional (2D) monolayer cultures; 2) further advances in 3D culture systems have led to the differentiation of iPSCs into organoids with multiple brain cell types and specific brain regions. These 3D organoids have gained widespread attention as in vitro tools to recapitulate complex features of the brain, and 3) Complex interactions between iPSC-derived brain cell types can recapitulate physiological and pathological conditions of blood-brain barrier (BBB). As iPSCs can be generated from diverse patient populations, researchers have effectively applied 2D, 3D and BBB models to recapitulate genetically complex neurological disorders and reveal novel insights into molecular and genetic mechanisms of neurological disorders. In this review, we describe recent progress in the generation of 2D, 3D and BBB models from iPSCs and further discuss their limitations, advantages, and future ventures. This review also covers the current status of applications of 2D, 3D and BBB models in drug screening, precision medicine, and modeling a wide range of neurological diseases (e.g., neurodegenerative diseases, neurodevelopmental disorders, brain injury, and neuropsychiatric disorders).

mRNAsi Index: Machine Learning in Mining Lung Adenocarcinoma Stem Cell Biomarkers

“…This process makes therapies ineffective for certain kinds of cancers [12]. As CSCs have been found and separated in several carcinomas, including lung cancer in vivo and in vitro [13], CSC research can provide ideas for solving the drug-resistant dilemma of lung cancer.…”

Ovine fetuses from slaughterhouses: a useful source for neural cell primary cultures

“…Indeed, the favorite animal models are those showing brain size, brain complexity, life span expectancy and diseases similar to those of humans [31, 32]. Human-derived cell cultures exist, including stem cell-derived primary neuronal and glial cultures, as well as sophisticated 3D organoids [23,24,25]. However, cultures from lots of animal species are also exploited as validated models.…”

“…Cell cultures carried out from sheep brain represent another important tool for studying neural cell biology instead of the usual cell cultures obtained from rats [18, 19, 20, 21, 22]. Actually, in addition to ovine cultured cells, human-derived cell models exist, including stem cell-derived primary neuronal and glial cultures, as well as sophisticated 3D organoids [23, 24, 25]. However, such models may be expensive and/or need a high degree of manipulation in order to get differentiated neural cells.…”

Stem Cell-Based Disease Modeling and Cell Therapy

“…iPSCs are artificial pluripotent stem cells and can be reprogrammed from many somatic cells such as skin and blood cells. iPSCs are similar to ESCs in the capacity of proliferation and differentiation [ 7 , 8 , 9 ]. Cancer stem cells are tumor-initiating clonogenic cells.…”

“…In particular, recent progress in the field of iPSCs has opened the doors to a new era of disease modelling. iPSCs can be generated from diverse patient populations, expanded, and differentiated into a disease-related specific cell types (e.g., neurons and cardiomyocytes) that can be either cultured as two-dimensional (2D) monolayers or included in stem cell-derived organoids, which can then be used as a tool to improve the understanding of disease mechanisms and to test therapeutic interventions [ 9 , 21 , 22 ].…”