Mesenchymal stem cells primed with valproate and lithium robustly migrate to infarcted regions and facilitate recovery in a stroke model.

Content Provider	Semantic Scholar
Author	Tsai, L. Wang, Zhifei Munasinghe, Jeeva Leng, Yan Leeds, Peter Chuang, D. C.-C.
Copyright Year	2011
Abstract	BACKGROUND AND PURPOSE The migratory efficiency of mesenchymal stem cells (MSC) toward cerebral infarct after transplantation is limited. Valproate (VPA) and lithium enhance in vitro migration of MSC by upregulating CXC chemokine receptor 4 and matrix metalloproteinase-9, respectively. Ability of VPA and lithium to promote MSC homing and to improve functional recovery was assessed in a rat model of cerebral ischemia. METHODS MSC primed with VPA (2.5 mmol/L, 3 hours) and/or lithium chloride (2.5 mmol/L, 24 hours) were transplanted into rats 24 hours after transient middle cerebral artery occlusion (MCAO). Neurological function was assessed via rotarod test, Neurological Severity Score, and body asymmetry test for 2 weeks. Infarct volume was analyzed by MRI. The number of homing MSC and microvessel density in the infarcted regions were measured 15 days after MCAO using immunohistochemistry. RESULTS Priming with VPA or lithium increased the number of MSC homing to the cerebral infarcted regions, and copriming with VPA and lithium further enhanced this effect. MCAO rats receiving VPA-primed and/or lithium-primed MSC showed improved functional recovery, reduced infarct volume, and enhanced angiogenesis in the infarcted penumbra regions. These beneficial effects of VPA or lithium priming were reversed by AMD3100, a CXC chemokine receptor 4 antagonist, and GM6001, a matrix metalloproteinase inhibitor, respectively. CONCLUSIONS Priming with VPA and/or lithium promoted the homing and migration ability of MSC, improved functional recovery, reduced brain infarct volume, and enhanced angiogenesis in a rat MCAO model. These effects were likely mediated by VPA-induced CXC chemokine receptor 4 overexpression and lithium-induced matrix metalloproteinase-9 upregulation.
Starting Page	115
Ending Page	132
Page Count	18
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://stroke.ahajournals.org/content/strokeaha/42/10/2932.full.pdf?download=true
Alternate Webpage(s)	http://stroke.ahajournals.org/content/strokeaha/early/2011/08/11/STROKEAHA.110.612788.full.pdf
PubMed reference number	21836090v1
Alternate Webpage(s)	https://doi.org/10.1161/STROKEAHA.110.612788
DOI	10.1161/strokeaha.110.612788
Journal	Stroke
Volume Number	42
Issue Number	10
Language	English
Access Restriction	Open
Subject Keyword	AMD3100 Bipolar Disorder CXCR4 Receptors Cerebral Infarction Cerebral Ischemia Cerebrovascular accident Chemokine CXCL11 Chloride Ion GM 6001 Lithium Chloride Matrix Metalloproteinase 9 Matrix Metalloproteinase Inhibitors Matrix Metalloproteinases Mesenchymal Stem Cells Metalloproteases Microvessels Middle Cerebral Artery Occlusion Occlusion of artery (disorder) Patients Priming Exercise Rotarod Performance Test Structure of cerebral artery Structure of middle cerebral artery Valproate chemokine receptor metalloendopeptidase inhibitor activity millimole
Content Type	Text
Resource Type	Article