Neuroprotective effects of mesenchymal stem cells derived from human embryonic stem cells in transient focal cerebral ischemia in rats

• Published in: Journal of cerebral blood flow and metabolism Vol. 29; no. 4; pp. 780 - 791
• Main Authors: Liu, Yi-Ping, Seçkin, Hakan, İzci, Yusuf, Du, Zhong Wei, Yan, Yi-Ping, Başkaya, Mustafa K
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.04.2009; Nature Publishing Group; Sage Publications Ltd
• Subjects: Animals; Biological and medical sciences; Cell Differentiation; Cell Movement; Embryonic Stem Cells - cytology; Endothelial Cells - cytology; Femoral Vein; Green Fluorescent Proteins; Humans; Immunophenotyping; Infarction, Middle Cerebral Artery; Ischemic Attack, Transient - therapy; Medical sciences; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - physiology; Neurology; Neurons - cytology; Neuropharmacology; Neuroprotective agent; Pharmacology. Drug treatments; Rats; Rats, Inbred SHR; Transplantation, Heterologous; Vascular diseases and vascular malformations of the nervous system; stroke; cerebral ischemia; mesenchymal stem cells; spontaneously hypertensive rats; human embryonic stem cells; Human; Hypertension; Stroke; Nervous system diseases; Rat; Rodentia; Cardiovascular disease; Cerebral disorder; Vascular disease; Vertebrata; Mammalia; Animal; Central nervous system disease; Brain ischemia; Cerebrovascular disease
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/jcbfm.2009.1

Embryonic mesenchymal stem cells (eMSCs) were first derived from human embryonic stem cells (hESCs) overexpressing green fluorescence protein (GFP). They expressed CD29, CD44, CD73, CD105, CD166 and nestin, but not CD34, CD45, CD106 SSEA-4 or Oct3/4. Twenty million eMSCs in 1mL of phosphate-buffered saline (PBS) were injected into the femoral veins of spontaneously hypertensive rats after transient middle cerebral artery occlusion. The migration and differentiation of the eMSCs in the ischemic brain were analyzed. The results revealed that eMSCs migrated to the infarction region and differentiated into neurons, which were positive for β-tubulin III, microtubule-associated protein 2 (MAP2), HuC, neurofilament and human nuclear antibody, and to vascular endothelial cells, which were positive for von Willebrand factor (vWF). The transplanted cells survived in the infarction region for at least 4 weeks. Adhesive removal function significantly improved in the first week after cell transplantation, and rotarod motor function significantly improved starting from the second week. The infarction volume in the eMSC group was significantly smaller than that in the PBS control group at 4 weeks after infusion. The results of this study show that when administered intravenously, eMSCs differentiated into neuronal and endothelial cells, reduced the infarction volume, and improved behavioral functional outcome significantly in transient focal cerebral ischemia.