Therapeutic benefits of human mesenchymal stem cells derived from bone marrow after global cerebral ischemia

• Published in: Brain research Vol. 1310; pp. 8 - 16
• Main Authors: Zheng, Wei, Honmou, Osamu, Miyata, Kei, Harada, Kuniaki, Suzuki, Junpei, Liu, He, Houkin, Kiyohiro, Hamada, Hirofumi, Kocsis, Jeffery D
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15.01.2010; Elsevier
• Subjects: Analysis of Variance; Animals; Biological and medical sciences; Bone marrow; Bone Marrow Cells - physiology; Brain Ischemia - complications; Brain Ischemia - surgery; Brain-Derived Neurotrophic Factor - metabolism; Cardiac arrest; Cell Count - methods; Creatine - metabolism; Disease Models, Animal; Global cerebral ischemia; Heart Arrest - etiology; Heart Arrest - therapy; Humans; In Situ Nick-End Labeling - methods; Lactic Acid - metabolism; Magnetic Resonance Imaging - methods; Male; Maze Learning - physiology; Medical sciences; Mesenchymal Stem Cell Transplantation - methods; Neurology; Neuroprotection; Rats; Rats, Wistar; Regeneration; Time Factors; Transplantation; Vascular diseases and vascular malformations of the nervous system; Bone marrow; Neuroprotection; Regeneration; Transplantation; Global cerebral ischemia; Cardiac arrest; Human; Nervous system diseases; Stem cell; Central nervous system; Cardiovascular disease; Cerebral disorder; Encephalon; Vascular disease; Treatment; Central nervous system disease; Brain ischemia; Cerebrovascular disease
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2009.11.012

Abstract Although intravenous delivery of mesenchymal stem cells (MSCs) prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat middle cerebral artery occlusion models, there are few reports of MSC treatment in global cerebral ischemia. We utilized a global cerebral ischemia model induced by arresting the heart with a combination of hypovolemia and intracardiac injections of a cold potassium chloride solution in order to study the potential therapeutic benefits of human mesenchymal stem cells (hMSCs) on global cerebral ischemia. hMSCs were intravenously injected into the rats 3 h after resuscitation from cardiac arrest. The effects on structural and functional outcome of hMSC were assessed at 5 h and 1, 3, and 7 days using magnetic resonance spectroscopy (MRS), histology, and cognitive functional analysis. Intravenous delivery of hMSCs reduced the Lac/Cr ratios, nuclear DNA fragmentation, neuronal loss, and elicited functional improvement compared with the control sham group. Enzyme-linked immunosorbent assay (ELISA) of the hippocampus revealed an increase in BDNF in hMSC-treated group. These data suggest that intravenous delivery of hMSC may have a therapeutic effect in global cerebral ischemia.