From Pluripotency to Precision: A Comprehensive Review of hPSCs/iPSCs Models in Neuroscience Research

Neurodevelopmental and neurodegenerative diseases involve critical abnormalities in pathogenesis. Even though there exists copious drugs and treatments, still a need for an effective model for absolute replication of disease pathophysiology and therapeutic drug discovery. This comprehensive systematic review amasses methods and approaches for developing neuronal models for neurological diseases using hPSCs/iPSCs. Abundant culturing methods, growth factors, modulators and toxins were utilised to induce the disease and were appraised. Research articles were traced from Google Scholar, PubMed/NIH, and Science Direct. Publications using hPSCs/iPSCs as differentiated neuronal disease models were screened using PRISMA guidelines, with designed inclusion and exclusion criteria. This protocol highlights the procedures for developing 2D and 3D neuronal models derived from hPSCs/iPSCs. 2D neuronal models include NPCs, NSCs, and neural rosettes, neurons, while 3D methods rely on embryoid bodies, neurospheres, spheroids and organoids due to the enhanced differentiation, survival and maturation of hPSCs/iPSCs. These processes include varied factors for culturing. Growth factors like GDNF, BDNF, cAMP, ascorbic acid, TGF-β, and Dual-SMAD inhibition. Post-analytical techniques like MEA, H&E, TEM, microscopy, immunoassays, and electrophysiology ensures the structural and functional endorsements. These models offer researchers a reliable platform to investigate the disease physiopathology and drug design for neurological disorders.