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Stem Cells Transl Med. 2017 May;6(5):1424-1433. doi: 10.1002/sctm.16-0438. Epub 2017 Mar 13.

Feasibility and Efficacy of Intra-Arterial Administration of Mesenchymal Stem Cells in an Animal Model of Double Toxin-Induced Multiple System Atrophy.

Author information

1
Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.
2
Severance Biomedical Science Institute, Yonsei University, Seoul, South Korea.
3
Bioengineering Institute, CORESTEM Inc., Gyeonggi, South Korea.

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 × 107 MSCs) 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.

KEYWORDS:

Efficacy; Feasibility; Intra-arterial injection; Mesenchymal stem cells; Multiple system atrophy

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