1. ¹Department of Neurological Surgery, School of Medicine and Public Health University of Wisconsin-Madison, Madison, Wisconsin, USA
2. ²Waisman Center, University of Wisconsin-Madison, Cell Culture, Madison, Wisconsin, USA
3. ³William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin, USA

Correspondence: Dr MK Bakaya, Department of Neurological Surgery, School of Medicine and Public Health University of Wisconsin-Madison, Box 8660 Clinical Science Center-K4, 600 Highland Ave, Madison, WI 53792, USA. E-mail: m.baskaya@neurosurg.wisc.edu

Received 8 July 2008; Revised 6 January 2009; Accepted 6 January 2009; Published online 11 February 2009.

Abstract

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 1 mL 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 -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.