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Feasibility and Efficacy of Intra-Arterial Administration of Embryonic Stem Cell Derived-Mesenchymal Stem Cells in Animal Model of Alzheimer's Disease

Authors
 Dong Yeol Kim  ;  Sung Hyun Choi  ;  Jee Sun Lee  ;  Hyoung Jun Kim  ;  Ha Na Kim  ;  Ji Eun Lee  ;  Jin Young Shin  ;  Phil Hyu Lee 
Citation
 JOURNAL OF ALZHEIMERS DISEASE, Vol.76(4) : 1281-1296, 2020-05 
Journal Title
 JOURNAL OF ALZHEIMERS DISEASE 
ISSN
 1387-2877 
Issue Date
2020-05
Keywords
Alzheimer’s disease ; autophagy ; intra-arterial injection ; mesenchymal stem cell ; protection
Abstract
Mesenchymal stem cells (MSCs) promote functional recoveries in pathological experimental models of the central nervous system and are currently being tested in clinical trials for neurological disorders. However, no studies have examined the various roles of embryonic stem cell derived (ES)-MSCs in eliciting therapeutic effects for Alzheimer's disease (AD). In the present study, we investigated the neuroprotective effect of ES-MSCs in cellular and animal models of AD, as well as the safety of the intra-arterial administration of ES-MSCs in an AD animal model. ES-MSCs displayed higher cell viability than that of bone marrow (BM)-MSCs in amyloid-β (Aβ)-induced cellular models. Moreover, the efficacy of autophagy induction in ES-MSCs was comparable to that of BM-MSCs; however, intracellular Aβ levels were more significantly reduced in ES-MSCs than in BM-MSCs. In a rat model of AD, ES-MSCs significantly inhibited Aβ-induced cell death in the hippocampus and promoted autophagolysosomal clearance of Aβ, which was concomitantly followed by decreased levels of Aβ in the hippocampus. Furthermore, ES-MSC treatment in Aβ-treated rats featured a higher memory performance than that of rats injected solely with Aβ. Finally, intra-arterial administration of an appropriate cell density of ES-MSCs was safe and free from in situ occlusion or cerebral ischemia. These data support the therapeutic potential of ES-MSCs and clinical applications of the intra-arterial route of ES-MSC administration in AD.
Full Text
https://content.iospress.com/articles/journal-of-alzheimers-disease/jad200026
DOI
10.3233/JAD-200026
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Shin, Jin Young(신진영)
Lee, Phil Hyu(이필휴) ORCID logo https://orcid.org/0000-0001-9931-8462
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/179996
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