Ng Neville, Newbery Michelle, Maksour Simon, Dottori Mirella, Sluyter Ronald, Ooi Lezanne
Illawarra Health and Medical Research Institute, Wollongong, NSW, Australia.
School of Chemistry and Molecular Bioscience and Molecular Horizons, University of Wollongong, Wollongong, NSW, Australia.
Front Cell Neurosci. 2022 May 11;16:858432. doi: 10.3389/fncel.2022.858432. eCollection 2022.
For neurological diseases, molecular and cellular research relies on the use of model systems to investigate disease processes and test potential therapeutics. The last decade has witnessed an increase in the number of studies using induced pluripotent stem cells to generate disease relevant cell types from patients. The reprogramming process permits the generation of a large number of cells but is potentially disadvantaged by introducing variability in clonal lines and the removal of phenotypes of aging, which are critical to understand neurodegenerative diseases. An under-utilized approach to disease modeling involves the transdifferentiation of aged cells from patients, such as fibroblasts or blood cells, into various neural cell types. In this review we discuss techniques used for rapid and efficient direct conversion to neural cell types. We examine the limitations and future perspectives of this rapidly advancing field that could improve neurological disease modeling and drug discovery.
对于神经疾病，分子和细胞研究依赖于使用模型系统来研究疾病过程并测试潜在的治疗方法。在过去十年中，使用诱导多能干细胞从患者中生成与疾病相关的细胞类型的研究数量有所增加。重编程过程能够产生大量细胞，但可能存在劣势，即引入克隆系的变异性以及消除衰老表型，而这些对于理解神经退行性疾病至关重要。一种未得到充分利用的疾病建模方法涉及将患者的衰老细胞，如成纤维细胞或血细胞，转分化为各种神经细胞类型。在这篇综述中，我们讨论了用于快速高效直接转化为神经细胞类型的技术。我们审视了这个快速发展领域的局限性和未来前景，该领域有望改善神经疾病建模和药物发现。
