title: Feasibility and Efficacy of Intra-Arterial Administration of Mesenchymal Stem Cells in an Animal Model of Double Toxin-Induced Multiple System Atrophy.
abstract: Multiple system atrophy (MSA) is a sporadic neurodegenerative disease of the central and autonomic nervous system. Because no drug treatment consistently benefits MSA patients, neuroprotective strategy using mesenchymal stem cells (MSCs) has a lot of concern for the management of MSA. In this study, we investigated the safety and efficacy of intra-arterial administration of MSCs via internal carotid artery (ICA) in an animal model of MSA. The study was composed of feasibility test using a ×10 and ×50 of a standard dose of MSCs (4 × 107MSCs) and efficacy test using a ×0.2, ×2, and ×20 of the standard dose. An ultrasonic flow meter and magnetic resonance imaging (MRI) showed that no cerebral ischemic lesions with patent ICA blood flow was were observed in animals receiving a ×10 of the standard dose of MSCs. However, no MSA animals receiving a ×50 of the standard dose survived. In efficacy test, animals injected with a ×2 of the standard dose increased nigrostriatal neuronal survival relative to a ×0.2 or ×20 of the standard dose. MSA animals receiving MSCs at ×0.2 and ×2 concentrations of the standard dose exhibited a significant reduction in rotation behavior relative to ×20 of the standard dose of MSCs. Cerebral ischemic lesions on MRI were only observed in MSA animals receiving a ×20 of the standard dose. The present study revealed that if their concentration is appropriate, intra-arterial injection of MSCs is safe and exerts a neuroprotective effect on striatal and nigral neurons with a coincidental improvement in motor behavior. Stem Cells Translational Medicine 2017;6:1424-1433.
authors.affiliation: Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.|Severance Biomedical Science Institute, Yonsei University, Seoul, South Korea.
authors.forename: Ha
authors.initials: H
authors.lastname: Na Kim
authors.affiliation: Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.|Severance Biomedical Science Institute, Yonsei University, Seoul, South Korea.
authors.forename: Dong
authors.initials: D
authors.lastname: Yeol Kim
authors.affiliation: Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.|Severance Biomedical Science Institute, Yonsei University, Seoul, South Korea.
authors.forename: Se
authors.initials: S
authors.lastname: Hee Oh
authors.affiliation: Bioengineering Institute, CORESTEM Inc., Gyeonggi, South Korea.
authors.forename: Hyung
authors.initials: H
authors.lastname: Sook Kim
authors.affiliation: Bioengineering Institute, CORESTEM Inc., Gyeonggi, South Korea.
authors.forename: Kyung
authors.initials: K
authors.lastname: Suk Kim
authors.affiliation: Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.|Severance Biomedical Science Institute, Yonsei University, Seoul, South Korea.
authors.forename: Phil
authors.initials: P
authors.lastname: Hyu Lee
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D019578:Multiple System Atrophy / Q000000981:diagnostic imaging / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: Efficacy; Feasibility; Intra-arterial injection; Mesenchymal stem cells; Multiple system atrophy