Development of brain organoid technology derived from iPSC for the neurodegenerative disease modelling: a glance through

Abstract

Neurodegenerative diseases are adult-onset neurological conditions that are notoriously difficult to model for drug discovery and development because most models are unable to accurately recapitulate pathology in disease-relevant cells, making it extremely difficult to explore the potential mechanisms underlying neurodegenerative diseases. Therefore, alternative models of human or animal cells have been developed to bridge the gap and allow the impact of new therapeutic strategies to be anticipated more accurately by trying to mimic neuronal and glial cell interactions and many more mechanisms. In tandem with the emergence of human-induced pluripotent stem cells which were first generated in 2007, the accessibility to human-induced pluripotent stem cells (hiPSC) derived from patients can be differentiated into disease-relevant neurons, providing an unrivaled platform for in vitro modeling, drug testing, and therapeutic strategy development. The recent development of three-dimensional (3D) brain organoids derived from iPSCs as the best alternative models for the study of the pathological features of neurodegenerative diseases. This review highlights the overview of current iPSC-based disease modeling and recent advances in the development of iPSC models that incorporate neurodegenerative diseases. In addition, a summary of the existing brain organoid-based disease modeling of Alzheimer’s disease was presented. We have also discussed the current methodologies of regional specific brain organoids modeled, its potential applications, emphasizing brain organoids as a promising platform for the modeling of patient-specific diseases, the development of personalized therapies, and contributing to the design of ongoing or future clinical trials on organoid technologies.

Neuroinflammation-on-a-chip for multiple sclerosis research: a narrative review

“…Embryonic stem cell transplantations in the clinical practice are being replaced by iPSC due to their significant efforts in understanding diseases and screening for potential medications intoxication. In fact, one of its advantages is the ability to implement it without the limitations of donor cells’ access upon investigation different diseases 41 .…”

Neurexin dysfunction in neurodevelopmental and neuropsychiatric disorders: a PRIMSA-based systematic review through iPSC and animal models

“…Herein lies the importance of in vitro human models, specifically induced pluripotent stem cells (iPSCs). By reprogramming somatic cells from patients into iPSCs, and subsequently differentiating these cells into neurons, researchers can create patient-specific neural models that recapitulate disease phenotypes ( Jusop et al, 2023 ). This approach allows for the study of neurexin dysfunction in a cellular context that closely mirrors the patient’s genetic and epigenetic background ( Lee et al, 2020 ).…”

Limitations of human brain organoids to study neurodegenerative diseases: a manual to survive

“…On the other hand, traditional monolayers can be generated with human cells but have inherent limitations in physiological relevance, such as unrealistically flattened dendrites ( Fabbri et al, 2023 ). In this context, brain organoids have been proposed as a promising alternative for studying neurodegeneration and bridging the gap between patient research and model organisms ( Figure 1 ; Adlakha, 2023 ; Jusop et al, 2023 ). These 3D cultures allow cells to establish more physiological connections, promoting cell division, extracellular matrix synthesis, and the acquisition of morphology and gene expression patterns that more closely resemble those of a human brain ( Tekin et al, 2018 ).…”