CRISPR/Cas9 Edited sRAGE-MSCs Protect Neuronal Death in Parkinson's Disease Model
- Author:
Jaesuk LEE
1
;
Delger BAYARSAIKHAN
;
Roshini ARIVAZHAGAN
;
Hyejung PARK
;
Byungyoon LIM
;
Peter GWAK
;
Goo Bo JEONG
;
Jaewon LEE
;
Kyunghee BYUN
;
Bonghee LEE
Author Information
- Publication Type:Original Article
- Keywords: Parkinson's disease; CRISPR/Cas9; sRAGE secreting UCB-MSC; Microglia; AGE-albumin
- MeSH: Animals; Behavior Rating Scale; Cell Death; Corpus Striatum; Mesenchymal Stromal Cells; Methods; Mice; Microglia; Models, Animal; Nervous System; Neurodegenerative Diseases; Neurons; Parkinson Disease; Rage; Substantia Nigra; Umbilical Cord
- From:International Journal of Stem Cells 2019;12(1):114-124
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND AND OBJECTIVES: Parkinson’s disease (PD) is a fatal and progressive degenerative disease of the nervous system. Until recently, its promising treatment and underlying mechanisms for neuronal death are poorly understood. This study was investigated to identify the molecular mechanism of neuronal death in the substantia nigra and corpus striatum of PD. METHODS: The soluble RAGE (sRAGE) secreting Umbilical Cord Blood—derived Mesenchymal Stem Cell (UCB-MSC) was generated by gene editing method using clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9). These cells were transplanted into Corpus Striatum of rotenone-induced PD animal models then behavioral test, morphological analysis, and immunohistochemical experiments were performed to determine the neuronal cell death and recovery of movement. RESULTS: The neuronal cell death in Corpus Striatum and Substantia Nigra was dramatically reduced and the movement was improved after sRAGE secreting UCB-MSC treatment in PD mice by inhibition of RAGE in neuronal cells. CONCLUSIONS: We suggest that sRAGE secreting UCB-MSC based therapeutic approach could be a potential treatment strategy for neurodegenerative disease including PD.
