title: Effects of Mesenchymal Stem Cell Treatment on the Expression of Matrix Metalloproteinases and Angiogenesis during Ischemic Stroke Recovery.
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 × 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.
authors.affiliation: Department of Neurology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.|Severance Integrative Research Institute for Cerebral & Cardiovascular Disease, Yonsei University Health System, Seoul, Korea.
authors.forename: Hyo Suk
authors.initials: HS
authors.lastname: Nam
authors.affiliation: Department of Neurology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.|Severance Integrative Research Institute for Cerebral & Cardiovascular Disease, Yonsei University Health System, Seoul, Korea.
authors.forename: Il
authors.initials: I
authors.lastname: Kwon
authors.affiliation: Department of Neurology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.|Severance Integrative Research Institute for Cerebral & Cardiovascular Disease, Yonsei University Health System, Seoul, Korea.
authors.forename: Bo Hyung
authors.initials: BH
authors.lastname: Lee
authors.affiliation: Department of Neurology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.|Severance Integrative Research Institute for Cerebral & Cardiovascular Disease, Yonsei University Health System, Seoul, Korea.
authors.forename: Haejin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Brain Korea 21 Plus Project for Medical Science, Yonsei University, Seoul, Korea.|Severance Integrative Research Institute for Cerebral & Cardiovascular Disease, Yonsei University Health System, Seoul, Korea.
authors.forename: Jayoung
authors.initials: J
authors.lastname: Kim
authors.affiliation: Brain Korea 21 Plus Project for Medical Science, Yonsei University, Seoul, Korea.|Severance Integrative Research Institute for Cerebral & Cardiovascular Disease, Yonsei University Health System, Seoul, Korea.
authors.forename: Sunho
authors.initials: S
authors.lastname: An
authors.affiliation: Department of Neurology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.|Severance Integrative Research Institute for Cerebral & Cardiovascular Disease, Yonsei University Health System, Seoul, Korea.
authors.forename: Ok-Hee
authors.initials: OH
authors.lastname: Lee
authors.affiliation: Department of Neurology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Phil Hyu
authors.initials: PH
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Severance Hospital, Yonsei Cell Therapy Center, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyun Ok
authors.initials: HO
authors.lastname: Kim
authors.affiliation: Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Hyun
authors.initials: H
authors.lastname: Namgoong
authors.affiliation: Department of Neurology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.|Severance Integrative Research Institute for Cerebral & Cardiovascular Disease, Yonsei University Health System, Seoul, Korea.
authors.forename: Young Dae
authors.initials: YD
authors.lastname: Kim
authors.affiliation: Department of Neurology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.|Severance Integrative Research Institute for Cerebral & Cardiovascular Disease, Yonsei University Health System, Seoul, Korea.
authors.forename: Ji Hoe
authors.initials: JH
authors.lastname: Heo
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D045442:Rotarod Performance Test; D020521:Stroke / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D020782:Matrix Metalloproteinases