Hayashi Yohei, Takami Miho, Matsuo-Takasaki Mami
iPS Advanced Characterization and Development Team, RIKEN BioResource Research Center, Tsukuba, Japan.
Front Cell Neurosci. 2020 Aug 13;14:224. doi: 10.3389/fncel.2020.00224. eCollection 2020.
Chromosomal abnormality causes congenital and acquired intractable diseases. In general, there are no fundamental treatments for these diseases. To establish platforms to develop therapeutics for these diseases, patient-derived induced pluripotent stem cells (iPSCs) are highly beneficial. To study abnormal chromosomal diseases, it is often hard to apply animal disease models because the chromosomal structures are variable among species. It is also difficult to apply simple genome editing technology in cells or individuals for abnormal chromosomes. Thus, these patient-derived iPSCs have advantages for developing disease models with multiple cell and tissue types, which are typically seen in the symptoms of abnormal chromosomal diseases. Here we review the studies of patient-derived iPSCs carrying abnormal chromosomes, focusing on pluripotent state and neural lineages. We also discuss the technological advances in chromosomal manipulations toward establishing experimental models and future therapeutics. Patient-derived iPSCs carrying chromosomal abnormality are valuable as cellular bioresources since they can indefinitely proliferate and provide various cell types. Also, these findings and technologies are important for future studies on elucidating pathogenesis, drug development, regenerative medicine, and gene therapy for abnormal chromosomal diseases.
染色体异常会导致先天性和后天性难治性疾病。一般来说，这些疾病没有根本性的治疗方法。为了建立针对这些疾病的治疗开发平台，患者来源的诱导多能干细胞（iPSC）非常有益。为了研究染色体异常疾病，由于染色体结构在物种间存在差异，往往很难应用动物疾病模型。在细胞或个体中对异常染色体应用简单的基因组编辑技术也很困难。因此，这些患者来源的iPSC在开发具有多种细胞和组织类型的疾病模型方面具有优势，这在染色体异常疾病的症状中很常见。在这里，我们回顾了携带异常染色体的患者来源iPSC的研究，重点关注多能状态和神经谱系。我们还讨论了在染色体操作方面的技术进展，以建立实验模型和未来的治疗方法。携带染色体异常的患者来源iPSC作为细胞生物资源很有价值，因为它们可以无限增殖并提供各种细胞类型。此外，这些发现和技术对于未来阐明染色体异常疾病的发病机制、药物开发、再生医学和基因治疗的研究很重要。
