Research Report Implantation of human umbilical cord-derived mesenchymal stem cells as a neuroprotective therapy for ischemic stroke in rats Seong-Ho Koh a,1 , Kyung Suk Kim b,c,1 , Mi Ran Choi c , Kyoung Hwa Jung d , Kyoung Sun Park d , Young Gyu Chai d , Wonjae Roh e , Se Jin Hwang f , Hyun-Ju Ko g , Yong-Min Huh g , Hee-Tae Kim a , Seung Hyun Kim a,b, ⁎ a Department of Neurology, Hanyang University, Seoul, 139-791, Korea b Institute of Biomedical Science, Hanyang University, Seoul, 139-791, Korea c Bioengineering Institute, CoreStem Inc., Chungbuk Province, 363-792, Korea d Department of Biochemistry, Division of Molecular and Life Sciences, Hanyang University, Ansan, 425-791, Korea e Roh Women’s Hospital, Seoul, 151-010, Korea f Department of Anatomy, College of Medicine, Hanyang University, Seoul, 139-791, Korea g Department of Radiology and Department of Biochemistry and Molecular Biology, Yonsei University, Seoul 120-752, Korea ARTICLE INFO ABSTRACT Article history: Accepted 18 June 2008 Available online 2 July 2008 In the present study, we examined the neuroprotective effects and mechanisms of implanted human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in ischemic stroke. hUC- MSCs were isolated from the endothelial/subendothelial layers of the human umbilical cord and cultured. Twenty days after the induction of in vitro neuronal differentiation, about 77.4% of the inoculated hUC-MSCs displayed morphological features of neurons and expressed neuronal cell markers like TU-20, Trk A, NeuN, and NF-M. However, functionally active neuronal type channels were not detected by electrophysiological examination. Before, during, or one day after in vitro neuronal differentiation, the hUC-MSCs produced granulocyte- colony stimulating factor, vascular endothelial growth factor, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor. In an in vivo study, implantation of the hUC-MSCs into the damaged hemisphere of immunosuppressed ischemic stroke rats improved neurobehavioral function and reduced infarct volume relative to control rats. Three weeks after implantation, most of the implanted hUC-MSCs were present in the damaged hemisphere; some of these cells expressed detectable levels of neuron-specific markers. Nestin expression in the hippocampus was increased in the hUC-MSC-implanted group relative to the control group. Since the hUC-MSCs were both morphologically differentiated into neuronal cells and able to produce neurotrophic factors, but had not become functionally active neuronal cells, the improvement in neurobehavioral function and the reduction of infarct volume might be related to the neuroprotective effects of hUC-MSCs rather than the formation of a new network between host neurons and the implanted hUC-MSCs. © 2008 Elsevier B.V. All rights reserved. Keywords: Stroke Cell therapy Adult stem cells Umbilical cord Neuroprotection BRAIN RESEARCH 1229 (2008) 233 – 248 ⁎ Corresponding author. Department of Neurology, College of Medicine, Hanyang University, #17 Haengdang-dong, Seongdong-gu, Seoul, 133-791, Korea. Fax: +82 2 2296 8370. E-mail address: kimsh1@hanyang.ac.kr (S.H. Kim). 1 Both authors contributed equally to this work. 0006-8993/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2008.06.087 available at www.sciencedirect.com www.elsevier.com/locate/brainres