Verma Isha, Seshagiri Polani B
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, 560012, India.
Department of Neurology, University of Michigan, Ann Arbor, 48109, USA.
Stem Cell Rev Rep. 2025 Apr 5. doi: 10.1007/s12015-025-10851-6.
Many neurological diseases involving tissue damage cannot be treated with drug-based approaches, and the inaccessibility of human brain samples further hampers the study of these diseases. Human pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), provide an excellent model for studying neural development and function. PSCs can be differentiated into various neural cell types, providing a renewal source of functional human brain cells. Therefore, PSC-derived neural cells are increasingly used for multiple applications, including neurodevelopmental and neurotoxicological studies, neurological disease modeling, drug screening, and regenerative medicine. In addition, the neural cells generated from patient iPSCs can be used to study patient-specific disease signatures and progression. With the recent advances in genome editing technologies, it is possible to remove the disease-related mutations in the patient iPSCs to generate corrected iPSCs. The corrected iPSCs can differentiate into neural cells with normal physiological functions, which can be used for autologous transplantation. This review highlights the current progress in using PSCs to understand the fundamental principles of human neurodevelopment and dissect the molecular mechanisms of neurological diseases. This knowledge can be applied to develop better drugs and explore cell therapy options. We also discuss the basic requirements for developing cell transplantation therapies for neurological disorders and the current status of the ongoing clinical trials.
许多涉及组织损伤的神经疾病无法通过基于药物的方法进行治疗，而获取人脑样本的困难进一步阻碍了对这些疾病的研究。人类多能干细胞（PSC），包括胚胎干细胞（ESC）和诱导多能干细胞（iPSC），为研究神经发育和功能提供了一个极佳的模型。PSC可以分化为各种神经细胞类型，提供功能性人脑细胞的更新来源。因此，PSC衍生的神经细胞越来越多地用于多种应用，包括神经发育和神经毒理学研究、神经疾病建模、药物筛选和再生医学。此外，从患者iPSC产生的神经细胞可用于研究患者特异性的疾病特征和进展。随着基因组编辑技术的最新进展，有可能去除患者iPSC中的疾病相关突变以产生校正后的iPSC。校正后的iPSC可以分化为具有正常生理功能的神经细胞，可用于自体移植。本综述强调了利用PSC来理解人类神经发育基本原理和剖析神经疾病分子机制的当前进展。这些知识可应用于开发更好的药物和探索细胞治疗方案。我们还讨论了开发神经疾病细胞移植疗法的基本要求以及正在进行的临床试验的现状。
