Feasibility and efficacy of intra-arterial administration of mesenchymal stem cells in an animal model of double toxin-induced multiple system atrophy

Ha Na Kim, Dong Yeol Kim, Se Hee Oh, Hyung Sook Kim, Kyung Suk Kim, Phil Hyu Lee

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Abstract

Multiple system atrophy (MSA) is a sporadic neurodegenerative disease of the central and auto-nomic 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.

Original languageEnglish
Pages (from-to)1424-1433
Number of pages10
JournalStem Cells Translational Medicine
Volume6
Issue number5
DOIs
Publication statusPublished - 2017 May

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All Science Journal Classification (ASJC) codes

  • Developmental Biology
  • Cell Biology

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