期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 18, 期 1, 页码 -出版社
MDPI AG
DOI: 10.3390/ijms18010224
关键词
Parkinson's disease; induced neural stem cell; differentiation; reprogramming; transplantation; functional recovery
资金
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, information and communications technology (ICT) and future Planning [NRF-2014R1A2A1A11050236, NRF-2014R1A2A1A11050248]
- Korea Health Technology R& D Project through the Korea Health Industry Development Institute (KHIDI)
- Ministry of Health & Welfare, Republic of Korea [HI14C2339]
- Bio & Medical Technology Development Program of the NRF
- Korean Government, MSIP [2015M3A9C7030091]
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.
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