2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling

Abstract

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there are no therapeutic cures available. Even though animal and histological models have been of great aid in understanding disease mechanisms and identifying possible therapeutic strategies, in order to find disease-modifying solutions there is still a critical need for systems that can provide more predictive and physiologically relevant results. One possible avenue is the development of patient-derived models, e.g. by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), which can then be differentiated into any cell type for modelling. These systems contain key genetic information from the donors, and therefore have enormous potential as tools in the investigation of pathological mechanisms underlying disease phenotype, and progression, as well as in drug testing platforms. hiPSCs have been widely cultured in 2D systems, but in order to mimic human brain complexity, 3D models have been proposed as a more advanced alternative. This review will focus on the use of patient-derived hiPSCs to model AD, PD, HD and ALS. In brief, we will cover the available stem cells, types of 2D and 3D culture systems, existing models for neurodegenerative diseases, obstacles to model these diseases in vitro, and current perspectives in the field.

Keywords: 3D culture; Human induced pluripotent stem cells; Neurodegenerative disease.

Fig. 1

Human induced pluripotent stem cells (hiPSCs) in neurodegenerative diseases modelling. Patient-derived somatic cells (SCs) can be genetically reprogrammed to generate iPSCs. High-tech systems can be used to culture and differentiate iPSCs into brain cells such as oligodendrocytes, astrocytes and different neuronal populations (NPs), providing the possibility to accurately study neurodegenerative diseases in vitro and to obtain essential information about disease phenotype and pathology insights. This strategy provides the possibility of testing drugs in vitro and identifying new therapies for incurable disorders such as Alzheimer’s (AD), Parkinson’s (PD), Huntington’s (HD) diseases and amyotrophic lateral sclerosis (ALS). (Illustrations obtained from https://smart.servier.com/)