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, philhyu Lee, Hyun Ok Kim, Hyun Namgoong, Young Dae Kim, Jihoe Heo

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Abstract

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.

Original languageEnglish
Article numbere0144218
JournalPloS one
Volume10
Issue number12
DOIs
Publication statusPublished - 2015 Dec 1

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metalloproteinases
angiogenesis
Stem cells
Matrix Metalloproteinases
Mesenchymal Stromal Cells
stroke
Middle Cerebral Artery Infarction
stem cells
Stroke
Mesenchymal Stem Cell Transplantation
Recovery
Matrix Metalloproteinase 2
arteries
Blood Vessels
blood vessels
cell transplantation
gelatinase A
Matrix Metalloproteinase 9
Infarction
gelatinase B

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Nam, Hyo Suk ; Kwon, Il ; Lee, Bo Hyung ; Kim, Haejin ; Kim, Jayoung ; An, Sunho ; Lee, Ok Hee ; Lee, philhyu ; Kim, Hyun Ok ; Namgoong, Hyun ; Kim, Young Dae ; Heo, Jihoe. / Effects of mesenchymal stem cell treatment on the expression of matrix metalloproteinases and angiogenesis during ischemic stroke recovery. In: PloS one. 2015 ; Vol. 10, No. 12.
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abstract = "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.",
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Effects of mesenchymal stem cell treatment on the expression of matrix metalloproteinases and angiogenesis during ischemic stroke recovery. / Nam, Hyo Suk; Kwon, Il; Lee, Bo Hyung; Kim, Haejin; Kim, Jayoung; An, Sunho; Lee, Ok Hee; Lee, philhyu; Kim, Hyun Ok; Namgoong, Hyun; Kim, Young Dae; Heo, Jihoe.

In: PloS one, Vol. 10, No. 12, e0144218, 01.12.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of mesenchymal stem cell treatment on the expression of matrix metalloproteinases and angiogenesis during ischemic stroke recovery

AU - Nam, Hyo Suk

AU - Kwon, Il

AU - Lee, Bo Hyung

AU - Kim, Haejin

AU - Kim, Jayoung

AU - An, Sunho

AU - Lee, Ok Hee

AU - Lee, philhyu

AU - Kim, Hyun Ok

AU - Namgoong, Hyun

AU - Kim, Young Dae

AU - Heo, Jihoe

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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.

AB - 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.

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