Combination therapy of stroke in rats with a nitric oxide donor and human bone marrow stromal cells enhances angiogenesis and neurogenesis

We tested the hypothesis that intravenous infusion of human marrow stromal cells (hMSC) with a nitric oxide donor, ( Z)-1-[ N-(2-aminoethyl)- N-(2-ammonioethyl) aminio] diazen-1-ium-1,2-diolate (DETA/NONOate), enhances angiogenesis, neurogenesis and neurological functional recovery after stroke in r...

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Published in:Brain research 2004-04, Vol.1005 (1), p.21-28
Main Authors: Chen, Jieli, Li, Yi, Zhang, Ruilan, Katakowski, Mark, Gautam, Subhash C., Xu, Yongxian, Lu, Mei, Zhang, Zhenggang, Chopp, Michael
Format: Article
Language:English
Subjects:
Angiogenesis
Animals
Biological and medical sciences
Bone Marrow Cells - cytology
Bone Marrow Cells - physiology
Bone marrow stromal cell
Bone Marrow Transplantation - methods
Drug Therapy, Combination
Humans
Infarction, Middle Cerebral Artery - drug therapy
Infarction, Middle Cerebral Artery - pathology
Infarction, Middle Cerebral Artery - surgery
Male
Medical sciences
Neovascularization, Physiologic - drug effects
Neovascularization, Physiologic - physiology
Neurogenesis
Neurology
Neurons - cytology
Neurons - drug effects
Neurons - physiology
Nitric oxide
Nitric Oxide Donors - pharmacology
Nitric Oxide Donors - therapeutic use
Rat
Rats
Rats, Wistar
Stroke
Stromal Cells - cytology
Stromal Cells - transplantation
Vascular diseases and vascular malformations of the nervous system
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Summary:We tested the hypothesis that intravenous infusion of human marrow stromal cells (hMSC) with a nitric oxide donor, ( Z)-1-[ N-(2-aminoethyl)- N-(2-ammonioethyl) aminio] diazen-1-ium-1,2-diolate (DETA/NONOate), enhances angiogenesis, neurogenesis and neurological functional recovery after stroke in rats compared to individual therapy. Experimental groups consist of rats subjected to 2 h of middle cerebral artery occlusion (MCAo) and at 24 h after MCAo intravenous injection of ( n=10/group): Group 1: phosphate buffered saline (PBS 1 ml) for control. Group 2: NONOate alone (0.4 mg/kg). Group 3: hMSCs (1×10 6) alone. Group 4: hMSCs (1×10 6) with NONOate (0.4 mg/kg). Functional tests and immunohistochemical staining were performed. Marginal functional recovery after treatment of stroke was found with 1×10 6 hMSCs alone ( p=0.06) and no benefit was detected with NONOate alone (0.4 mg/kg, p=0.64). However, NONOate+hMSCs in combination significantly induced functional recovery ( p
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2003.11.080