Choi Dong-Hee, Kim Ji-Hye, Kim Sung Min, Kang Kyuree, Han Dong Wook, Lee Jongmin
Department of Medical Science, School of Medicine, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, Korea.
Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, Korea.
Int J Mol Sci. 2017 Jan 22;18(1):224. doi: 10.3390/ijms18010224.
Parkinson's disease (PD) is a chronic, neurodegenerative disorder that results from the loss of cells in the substantia nigra (SN) which is located in the midbrain. However, no cure is available for PD. Recently, fibroblasts have been directly converted into induced neural stem cells (iNSCs) via the forced expression of specific transcription factors. Therapeutic potential of iNSC in PD has not been investigated yet. Here, we show that iNSCs directly converted from mouse fibroblasts enhanced functional recovery in an animal model of PD. The rotational behavior test was performed to assess recovery. Our results indicate that iNSC transplantation into the striatum of 6-hydroxydopamine (6-OHDA)-injected mice can significantly reduce apomorphine-induced rotational asymmetry. The engrafted iNSCs were able to survive in the striatum and migrated around the medial forebrain bundle and the SN pars compacta. Moreover, iNSCs differentiated into all neuronal lineages. In particular, the transplanted iNSCs that committed to the glial lineage were significantly increased in the striatum of 6-OHDA-injected mice. Engrafted iNSCs differentiated to dopaminergic (DA) neurons and migrated into the SN in the 6-OHDA lesion mice. Therefore, iNSC transplantation serves as a valuable tool to enhance the functional recovery in PD.
帕金森病（PD）是一种慢性神经退行性疾病，由位于中脑的黑质（SN）中的细胞丢失所致。然而，目前尚无治愈PD的方法。最近，通过强制表达特定转录因子，成纤维细胞已被直接转化为诱导神经干细胞（iNSCs）。iNSC在PD中的治疗潜力尚未得到研究。在此，我们表明从小鼠成纤维细胞直接转化而来的iNSCs可增强PD动物模型的功能恢复。通过旋转行为测试来评估恢复情况。我们的结果表明，将iNSC移植到注射了6-羟基多巴胺（6-OHDA）的小鼠纹状体中可显著降低阿扑吗啡诱导的旋转不对称性。移植的iNSCs能够在纹状体中存活，并在内侧前脑束和黑质致密部周围迁移。此外，iNSCs分化为所有神经元谱系。特别是，在注射了6-OHDA的小鼠纹状体中，分化为胶质谱系的移植iNSCs显著增加。在6-OHDA损伤小鼠中，移植的iNSCs分化为多巴胺能（DA）神经元并迁移到黑质中。因此，iNSC移植是增强PD功能恢复的一种有价值的工具。
