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Effects of Mesenchymal Stem Cell Treatment on the Expression of Matrix Metalloproteinases and Angiogenesis during Ischemic Stroke Recovery

 Hyo Suk Nam  ;  Il Kwon  ;  Bo Hyung Lee  ;  Haejin Kim  ;  Jayoung Kim  ;  Sunho An  ;  Ok-Hee Lee  ;  Phil Hyu Lee  ;  Hyun Ok Kim  ;  Hyun Namgoong  ;  Young Dae Kim  ;  Ji Hoe Heo 
 PLoS One, Vol.10(12) : e0144218, 2015 
Journal Title
 PLoS One 
Issue Date
Animals ; Brain Infarction/metabolism ; Brain Infarction/physiopathology ; Brain Infarction/therapy* ; Cells, Cultured ; Disease Models, Animal ; Humans ; Male ; Matrix Metalloproteinases/metabolism* ; Mesenchymal Stem Cell Transplantation/methods* ; Neovascularization, Pathologic/metabolism ; Neovascularization, Pathologic/therapy* ; Rats ; Rats, Sprague-Dawley ; Rotarod Performance Test ; Stroke/metabolism ; Stroke/physiopathology ; Stroke/therapy* ; Treatment Outcome
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 × 10(6), 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.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease (뇌심혈관질환융합연구사업단) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
권일(Kwon, Il) ORCID logo https://orcid.org/0000-0001-9449-5646
김영대(Kim, Young Dae) ORCID logo https://orcid.org/0000-0001-5750-2616
김자영(Kim, Ja Young)
김현옥(Kim, Hyun Ok) ORCID logo https://orcid.org/0000-0002-4964-1963
남효석(Nam, Hyo Suk) ORCID logo https://orcid.org/0000-0002-4415-3995
안선호(An, Sunho)
이보형(Lee, Bo Hyung)
이옥희(Lee, Ok Hee)
이필휴(Lee, Phil Hyu) ORCID logo https://orcid.org/0000-0001-9931-8462
허지회(Heo, Ji Hoe) ORCID logo https://orcid.org/0000-0001-9898-3321
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