한빛사논문
Hyunkyung Mo1,2, Juryun Kim3, Jennifer Yejean Kim4, Jang Woon Kim1, Heeju Han1,2, Si Hwa Choi1,2, Yeri Alice Rim1* and Ji Hyeon Ju1,3,5*
1Present Address: CiSTEM Laboratory, Catholic iPSC Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
2Department of Biomedicine and Health Science, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
3YiPSCELL, Inc, Omnibus Park, Banpo-daero 222, Seocho-gu, Seoul 06591, Republic of Korea.
4Department of Biology, Georgetown University, 3700 O St NW, Washington, DC 20057, USA.
5Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
*Correspondence: Yeri Alice Rim, Ji Hyeon Ju
Abstract
Background: Alzheimer's disease (AD) is the most common neurodegenerative disorder in the elderly, resulting in gradual destruction of cognitive abilities. Research on the development of various AD treatments is underway; however, no definitive treatment has been developed yet. Herein, we present induced pluripotent stem cell (iPSC)-derived cortical neural stem cell secretome (CNSC-SE) as a new treatment candidate for AD and explore its efficacy.
Methods: We first assessed the effects of CNSC-SE treatment on neural maturation and electromagnetic signal during cortical nerve cell differentiation. Then to confirm the efficacy in vivo, CNSC-SE was administered to the 5×FAD mouse model through the nasal cavity (5 μg/g, once a week, 4 weeks). The cell-mediated effects on nerve recovery, amyloid beta (Aβ) plaque aggregation, microglial and astrocyte detection in the brain, and neuroinflammatory responses were investigated. Metabolomics analysis of iPSC-derived CNSC-SE revealed that it contained components that could exert neuro-protective effects or amplify cognitive restorative effects.
Results: Human iPSC-derived CNSC-SE increased neuronal proliferation and dendritic structure formation in vitro. Furthermore, CNSC-SE-treated iPSC-derived cortical neurons acquired electrical network activity and action potential bursts. The 5×FAD mice treated with CNSC-SE showed memory restoration and reduced Aβ plaque accumulation.
Conclusions: Our findings suggest that the iPSC-derived CNSC-SE may serve as a potential, non-invasive therapeutic option for AD in reducing amyloid infiltration and restoring memory.
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