School of Biosystem and Biomedical Science, College of Health Science, Korea University, 22 Gil 6-3 Inchon-Ro, Seongbuk-Gu, Seoul 02855, Republic of Korea.
School of Biomedical Engineering, College of Health Science, Korea University, 7DaGil Inchon-ro, Seongbuk-gu, Seoul 02850, Republic of Korea; Department of Bio-Convergence Engineering, College of Health Science, Korea University, 7DaGil Inchon-ro, Seongbuk-gu, Seoul 02850, Republic of Korea.
Methods. 2018 Jan 15;133:104-112. doi: 10.1016/j.ymeth.2017.08.017. Epub 2017 Sep 1.
Therapeutic approaches based on stem cells have received considerable attention as potential treatments for Huntington's disease (HD), which is a fatal, inherited neurodegenerative disorder, caused by progressive loss of GABAergic medium spiny neurons (MSNs) in the striatum of the forebrain. Transplantation of stem cells or their derivatives in animal models of HD, efficiently improved functions by replacing the damaged or lost neurons. In particular, neural stem cells (NSCs) for HD treatments have been developed from various sources, such as the brain itself, the pluripotent stem cells (PSCs), and the somatic cells of the HD patients. However, the brain-derived NSCs are difficult to obtain, and the PSCs have to be differentiated into a population of the desired neuronal cells that may cause a risk of tumor formation after transplantation. In contrast, induced NSCs, derived from somatic cells as a new stem cell source for transplantation, are less likely to form tumors. Given that the stem cell transplantation strategy for treatment of HD, as a genetic disease, is to replace the dysfunctional or lost neurons, the correction of mutant genes containing the expanded CAG repeats is essential. In this review, we will describe the methods for obtaining the optimal NSCs for transplantation-based HD treatment and the differentiation conditions for the functional GABAergic MSNs as therapeutic cells. Also, we will discuss the valuable gene correction of the disease stem cells by the CRISPR/Cas9 system for HD treatment.
基于干细胞的治疗方法作为亨廷顿病 (HD) 的潜在治疗方法受到了相当大的关注，HD 是一种致命的遗传性神经退行性疾病，由大脑前脑纹状体中 GABA 能中间神经元 (MSNs) 的进行性丧失引起。在 HD 动物模型中，干细胞或其衍生物的移植通过替代受损或丢失的神经元，有效地改善了功能。特别是，用于 HD 治疗的神经干细胞 (NSCs) 已经从各种来源开发出来，例如大脑本身、多能干细胞 (PSCs) 和 HD 患者的体细胞。然而，脑源性 NSCs 难以获得，而 PSCs 必须分化为所需神经元细胞的群体，这可能会在移植后引起肿瘤形成的风险。相比之下，源自体细胞的诱导 NSCs 作为一种新的干细胞来源用于移植，不太可能形成肿瘤。鉴于干细胞移植策略作为一种遗传性疾病来治疗 HD，是为了替代功能失调或丢失的神经元，因此包含扩展 CAG 重复的突变基因的校正对于治疗至关重要。在这篇综述中，我们将描述用于获得最佳 NSCs 进行基于移植的 HD 治疗的方法，以及分化为功能性 GABA 能 MSNs 的条件作为治疗细胞。此外，我们将讨论 CRISPR/Cas9 系统对 HD 治疗中疾病干细胞的有价值的基因校正。
