International Journal of Stem Cells

Korean Society for Stem Cell Research (한국줄기세포학회)
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CRISPR/Cas9 Edited sRAGE-MSCs Protect Neuronal Death in Parkinson's Disease Model

  • Lee, Jaesuk (Center for Genomics and Proteomics & Stem Cell Core Facility, Lee Gil Ya Cancer and Diabetes Institute, Gachon University) ;
  • Bayarsaikhan, Delger (Center for Genomics and Proteomics & Stem Cell Core Facility, Lee Gil Ya Cancer and Diabetes Institute, Gachon University) ;
  • Arivazhagan, Roshini (Center for Genomics and Proteomics & Stem Cell Core Facility, Lee Gil Ya Cancer and Diabetes Institute, Gachon University) ;
  • Park, Hyejung (Center for Genomics and Proteomics & Stem Cell Core Facility, Lee Gil Ya Cancer and Diabetes Institute, Gachon University) ;
  • Lim, Byungyoon (Center for Genomics and Proteomics & Stem Cell Core Facility, Lee Gil Ya Cancer and Diabetes Institute, Gachon University) ;
  • Gwak, Peter (Center for Genomics and Proteomics & Stem Cell Core Facility, Lee Gil Ya Cancer and Diabetes Institute, Gachon University) ;
  • Jeong, Goo-Bo (Center for Genomics and Proteomics & Stem Cell Core Facility, Lee Gil Ya Cancer and Diabetes Institute, Gachon University) ;
  • Lee, Jaewon (Department of Aquatic Life Medicine, Pukyong National University) ;
  • Byun, Kyunghee (Center for Genomics and Proteomics & Stem Cell Core Facility, Lee Gil Ya Cancer and Diabetes Institute, Gachon University) ;
  • Lee, Bonghee (Center for Genomics and Proteomics & Stem Cell Core Facility, Lee Gil Ya Cancer and Diabetes Institute, Gachon University)
  • Received : 2018.11.15
  • Accepted : 2018.12.23
  • Published : 2019.03.31
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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.

Keywords

Acknowledgement

This study was supported by a National Research Foundation (NRF) grant (2017R1A2A2A01005212, NRF-2017M3A9B4028208, NRF-2017M3A9B4061408) and Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI13C2098).

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