ICVS-Life and Health Sciences Research Institute, School of Medicine, University of Minho, 4710-057 Braga, Portugal.
ICVS/3Bs-PT Government Associate Laboratory, 4710-057 Braga, Portugal.
Cells. 2023 Feb 7;12(4):538. doi: 10.3390/cells12040538.
Neurodevelopmental disorders (NDDs) arise from the disruption of highly coordinated mechanisms underlying brain development, which results in impaired sensory, motor and/or cognitive functions. Although rodent models have offered very relevant insights to the field, the translation of findings to clinics, particularly regarding therapeutic approaches for these diseases, remains challenging. Part of the explanation for this failure may be the genetic differences-some targets not being conserved between species-and, most importantly, the differences in regulation of gene expression. This prompts the use of human-derived models to study NDDS. The generation of human induced pluripotent stem cells (hIPSCs) added a new suitable alternative to overcome species limitations, allowing for the study of human neuronal development while maintaining the genetic background of the donor patient. Several hIPSC models of NDDs already proved their worth by mimicking several pathological phenotypes found in humans. In this review, we highlight the utility of hIPSCs to pave new paths for NDD research and development of new therapeutic tools, summarize the challenges and advances of hIPSC-culture and neuronal differentiation protocols and discuss the best way to take advantage of these models, illustrating this with examples of success for some NDDs.
神经发育障碍（NDDs）是由于大脑发育过程中高度协调的机制受到干扰而引起的，导致感觉、运动和/或认知功能受损。尽管啮齿动物模型为该领域提供了非常相关的见解，但将研究结果转化为临床应用，特别是针对这些疾病的治疗方法，仍然具有挑战性。造成这种失败的部分原因可能是遗传差异——一些目标在物种之间没有保守性，最重要的是，基因表达的调控存在差异。这促使人们使用源自人类的模型来研究 NDDS。人类诱导多能干细胞（hIPSCs）的产生为克服物种限制提供了一个新的合适选择，允许在保持供体患者遗传背景的同时研究人类神经元发育。几种 NDDs 的 hIPSC 模型已经通过模拟在人类中发现的几种病理表型证明了它们的价值。在这篇综述中，我们强调了 hIPSCs 在为 NDD 研究和新治疗工具的开发开辟新途径的实用性，总结了 hIPSC 培养和神经元分化方案的挑战和进展，并讨论了利用这些模型的最佳方法，用一些 NDD 的成功案例来说明这一点。
