Induced pluripotent stem cell models for advancing neurodevelopmental disorder research and regenerative medicine: a narrative review

Naffaa, Moawiah M*

Department of Psychology and Neuroscience, Duke University, Durham, NC, USA

*Correspondence to: Moawiah M Naffaa, PhD, Moawiah.naffaa@duke.edu.

Abstract

Induced pluripotent stem cell technology has significantly advanced regenerative medicine, providing an invaluable platform for modeling neurodevelopmental disorders and facilitating the development of novel therapeutic strategies. This article discusses the potential of induced pluripotent stem cells to unravel the cellular mechanisms underlying neurodevelopmental disorders, which, despite their genetic diversity, share common pathological features. Traditional models have struggled to replicate human-specific phenotypes, whereas induced pluripotent stem cell-based models, including two-dimensional cultures and three-dimensional organoids, offer more accurate representations of neural development and disease. The article explores advances in reprogramming and differentiation protocols that have enabled the generation of patient-specific induced pluripotent stem cell models, while acknowledging the challenges that persist, such as genomic instability and reprogramming inefficiencies. Additionally, the integration of CRISPR/Cas9 gene editing and patient-derived models has led to precision therapies targeting specific genetic mutations, including small molecules, gene editing, and antisense oligonucleotides. By combining in vitro and in vivo approaches, induced pluripotent stem cell-induced pluripotent stem cell models have expanded our understanding of neurodevelopmental disorder mechanisms, including aging, sex differences, and epigenetic regulation. However, challenges in model reproducibility and physiological complexity remain, and the article emphasizes efforts to address these limitations through optimized differentiation protocols, robust quality control, and ethical sourcing. Ultimately, induced pluripotent stem cells hold transformative potential for elucidating neurodevelopmental disorder pathogenesis and advancing personalized therapies for these complex disorders.

推进神经发育障碍研究和再生医学发展的诱导多能干细胞模型：叙述性综述

摘要

诱导多能干细胞技术极大地推动了再生医学的发展，为神经发育障碍建模提供了宝贵的平台，促进了新型治疗策略的开发。尽管神经发育障碍具有遗传多样性，但其病理特征却具有共性。文章讨论了诱导多能干细胞在揭示神经发育障碍的细胞机制方面的潜力。传统模型难以复制人类特异性表型，而基于诱导多能干细胞的模型，包括二维（2D）培养物和三维（3D）有机体，能更准确地反映神经发育和疾病。文章探讨了重编程和分化方案的进展，这些进展使患者特异性诱导多能干细胞模型得以产生，同时也承认了持续存在的挑战，如基因组不稳定性和重编程效率低下。此外，CRISPR/Cas9 基因编辑与患者衍生模型的结合，也带来了针对特定基因突变的精准疗法，包括小分子、基因编辑和反义寡核苷酸。通过结合体外和体内方法，诱导多能干细胞诱导多能干细胞模型扩展了我们对神经发育障碍机制的理解，包括衰老、性别差异和表观遗传调控。然而，模型的可重复性和生理复杂性仍面临挑战，文章强调了通过优化分化方案、健全的质量控制和道德采购来解决这些局限性的努力。最终，诱导多能干细胞在阐明神经发育障碍发病机制和推进针对这些复杂疾病的个性化疗法方面具有变革潜力。