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

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

Engineering Human Brain Organoids: From Basic Research to Tissue Regeneration

Background: Brain organoids are self-organized from human pluripotent stem cells and developed into various brain region following the developmental process of brain. Brain organoids provide promising approach for studying brain development process and neurological diseases and for tissue regeneration. Methods: In this review, we summarized the development of brain organoids technology, potential applications focusing on disease modeling for regeneration medicine, and multidisciplinary approaches to overcome current limitations of the technology. Results: Generations of brain organoids are categorized into two major classes by depending on the patterning method. In order to guide the differentiation into specific brain region, the extrinsic factors such as growth factors, small molecules, and biomaterials are actively studied. For better modelling of diseases with brain organoids and clinical application for tissue regeneration, improvement of the brain organoid maturation is one of the most important steps. Conclusion: Brain organoids have potential to develop into an innovative platform for pharmacological studies and tissue engineering. However, they are not identical replicas of their in vivo counterpart and there are still a lot of limitations to move forward to clinical applications