Adult Stem Cell Research Center and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
Animal Research and Molecular Imaging Center, Samsung Medical Center, Seoul 06351, Korea.
J Vet Sci. 2021 Jan;22(1):e7. doi: 10.4142/jvs.2021.22.e7.
Niemann-Pick disease type C (NPC) is caused by the mutation of genes, which leads to the abnormal accumulation of unesterified cholesterol and glycolipids in lysosomes. This autosomal recessive disease is characterized by liver dysfunction, hepatosplenomegaly, and progressive neurodegeneration. Recently, the application of induced neural stem cells (iNSCs), converted from fibroblasts using specific transcription factors, to repair degenerated lesions has been considered a novel therapy.
The therapeutic effects on NPC by human iNSCs generated by our research group have not yet been studied ; in this study, we investigate those effects.
We used an NPC mouse model to efficiently evaluate the therapeutic effect of iNSCs, because neurodegeneration progress is rapid in NPC. In addition, application of human iNSCs from NPC patient-derived fibroblasts in an NPC model can give insight into the clinical usefulness of iNSC treatment. The iNSCs, generated from NPC patient-derived fibroblasts using the SOX2 and HMGA2 reprogramming factors, were transplanted by intracerebral injection into NPC mice.
Transplantation of iNSCs showed positive results in survival and body weight change . Additionally, iNSC-treated mice showed improved learning and memory in behavior test results. Furthermore, through magnetic resonance imaging and histopathological assessments, we observed delayed neurodegeneration in NPC mouse brains.
iNSCs converted from patient-derived fibroblasts can become another choice of treatment for neurodegenerative diseases such as NPC.
尼曼-匹克病 C 型（NPC）是由基因突变引起的，导致溶酶体中未酯化胆固醇和糖脂的异常积累。这种常染色体隐性遗传病的特征是肝功能障碍、肝脾肿大和进行性神经退行性变。最近，使用特定转录因子将成纤维细胞转化为诱导性神经干细胞（iNSCs）来修复退化病变被认为是一种新的治疗方法。
本研究组生成的人诱导性神经干细胞（iNSCs）对 NPC 的治疗效果尚未进行研究；在本研究中，我们对此进行了探讨。
我们使用 NPC 小鼠模型来高效评估 iNSCs 的治疗效果，因为 NPC 中的神经退行性变进展迅速。此外，将来自 NPC 患者成纤维细胞的人 iNSCs 应用于 NPC 模型中可以深入了解 iNSC 治疗的临床实用性。使用 SOX2 和 HMGA2 重编程因子将 NPC 患者成纤维细胞转化为 iNSCs，然后通过脑内注射将其移植入 NPC 小鼠体内。
iNSC 移植显示出在存活和体重变化方面的积极结果。此外，iNSC 治疗的小鼠在行为测试结果中表现出改善的学习和记忆能力。此外，通过磁共振成像和组织病理学评估，我们观察到 NPC 小鼠大脑中的神经退行性变得到了延迟。
从患者成纤维细胞转化而来的 iNSCs 可以成为 NPC 等神经退行性疾病治疗的另一种选择。
