title: Implantation of human umbilical cord-derived mesenchymal stem cells as a neuroprotective therapy for ischemic stroke in rats.
abstract: 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.
authors.affiliation: Department of Neurology, Hanyang University, Seoul, 139-791, Korea.
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Koh
authors.forename: Kyung Suk
authors.initials: KS
authors.lastname: Kim
authors.forename: Mi Ran
authors.initials: MR
authors.lastname: Choi
authors.forename: Kyoung Hwa
authors.initials: KH
authors.lastname: Jung
authors.forename: Kyoung Sun
authors.initials: KS
authors.lastname: Park
authors.forename: Young Gyu
authors.initials: YG
authors.lastname: Chai
authors.forename: Wonjae
authors.initials: W
authors.lastname: Roh
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Ko
authors.forename: Yong-Min
authors.initials: YM
authors.lastname: Huh
authors.forename: Hee-Tae
authors.initials: HT
authors.lastname: Kim
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000473:pathology / Q000601:surgery; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D020521:Stroke / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D015703:Antigens, CD; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D018698:Glutamic Acid