Background: The efficacy of mesenchymal stem cell (MSC) transplantation in ischemic stroke might depend on the timing of administration. We investigated the optimal time point of MSC transplantation. After MSC treatment, we also investigated the expression of matrix metalloproteinases (MMPs), which play a role in vascular and tissue remodeling. Methods: Human bone marrow-derived MSCs (2 × 106, passage 5) were administrated intravenously after permanent middle cerebral artery occlusion (MCAO) was induced in male Sprague-Dawley rats. First, we determined the time point of MSC transplantation that led to maximal neurological recovery at 1 h, 1 day, and 3 days after MCAO. Next, we measured activity of MMP-2 and MMP-9, neurological recovery, infarction volume, and vascular density after transplanting MSCs at the time that led to maximal neurological recovery. Results: Among the MSC-transplanted rats, those of the MSC 1-hour group showed maximal recovery in the rotarod test (P = 0.023) and the Longa score (P = 0.018). MMP-2 activity at 1 day after MCAO in the MSC 1-hour group was significantly higher than that in the control group (P = 0.002), but MMP-9 activity was not distinct. The MSC 1-hour group also showed smaller infarction volume and higher vascular density than did the control group. Conclusions: In a permanent model of rodent MCAO, very early transplantation of human MSCs (1 h after MCAO) produced greater neurological recovery and decreased infraction volume. The elevation of MMP-2 activity and the increase in vascular density after MSC treatment suggest that MSCs might help promote angiogenesis and lead to neurological improvement during the recovery phase after ischemic stroke.
Bibliographical noteFunding Information:
This study was supported by a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (HI08C2149) (JHH), a grant from the Korea Government Ministry of Education, Science and Technology under Grant (2009-0069165) (HSN), a Korea Research Foundation Grant funded by the Korean Government (KRF-2007-331-E00126) (HSN), a faculty research grant from Yonsei University College of Medicine for 2011 (6-2011-0095) (HSN), and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2014R1A1A1005913) (IK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
© 2015 Nam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)