PMID- 18634757 OWN - NLM STAT- MEDLINE DCOM- 20090203 LR - 20181201 IS - 0006-8993 (Print) IS - 0006-8993 (Linking) VI - 1229 DP - 2008 Sep 10 TI - Implantation of human umbilical cord-derived mesenchymal stem cells as a neuroprotective therapy for ischemic stroke in rats. PG - 233-48 LID - 10.1016/j.brainres.2008.06.087 [doi] AB - 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. FAU - Koh, Seong-Ho AU - Koh SH AD - Department of Neurology, Hanyang University, Seoul, 139-791, Korea. FAU - Kim, Kyung Suk AU - Kim KS FAU - Choi, Mi Ran AU - Choi MR FAU - Jung, Kyoung Hwa AU - Jung KH FAU - Park, Kyoung Sun AU - Park KS FAU - Chai, Young Gyu AU - Chai YG FAU - Roh, Wonjae AU - Roh W FAU - Hwang, Se Jin AU - Hwang SJ FAU - Ko, Hyun-Ju AU - Ko HJ FAU - Huh, Yong-Min AU - Huh YM FAU - Kim, Hee-Tae AU - Kim HT FAU - Kim, Seung Hyun AU - Kim SH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080702 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Antigens, CD) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Nerve Tissue Proteins) RN - 3KX376GY7L (Glutamic Acid) SB - IM MH - Animals MH - Antigens, CD/metabolism MH - Cell Count MH - Cell Differentiation/drug effects MH - Cells, Cultured MH - Disease Models, Animal MH - Glutamic Acid/pharmacology MH - Hippocampus/pathology/surgery MH - Humans MH - Intercellular Signaling Peptides and Proteins/pharmacology MH - Membrane Potentials/drug effects/physiology/radiation effects MH - Mesenchymal Stem Cell Transplantation/*methods MH - Mesenchymal Stem Cells/*physiology MH - Nerve Tissue Proteins/metabolism MH - Neurons/metabolism MH - Patch-Clamp Techniques MH - Rats MH - Rats, Sprague-Dawley MH - Severity of Illness Index MH - Stroke/pathology/*therapy MH - Time Factors MH - Umbilical Cord/*cytology EDAT- 2008/07/19 09:00 MHDA- 2009/02/04 09:00 CRDT- 2008/07/19 09:00 PHST- 2008/03/13 00:00 [received] PHST- 2008/06/17 00:00 [revised] PHST- 2008/06/18 00:00 [accepted] PHST- 2008/07/19 09:00 [pubmed] PHST- 2009/02/04 09:00 [medline] PHST- 2008/07/19 09:00 [entrez] AID - S0006-8993(08)01527-8 [pii] AID - 10.1016/j.brainres.2008.06.087 [doi] PST - ppublish SO - Brain Res. 2008 Sep 10;1229:233-48. doi: 10.1016/j.brainres.2008.06.087. Epub 2008 Jul 2.