title: Implantation of olfactory ensheathing cells promotes neuroplasticity in murine models of stroke.
abstract: Murine olfactory ensheathing cells (OECs) promote central nervous system axonal regeneration in models of spinal cord injury. We investigated whether OECs could induce a neuroplastic effect to improve the neurological dysfunction caused by hypoxic/ischemic stress. In this study, human OECs/olfactory nerve fibroblasts (hOECs/ONFs) specifically secreted trophic factors including stromal cell-derived factor-1alpha (SDF-1alpha). Rats with intracerebral hOEC/ONF implantation showed more improvement on behavioral measures of neurological deficit following stroke than control rats. [18F]fluoro-2-deoxyglucose PET (FDG-PET) showed increased glucose metabolic activity in the hOEC/ONF-treated group compared with controls. In mice, transplanted hOECs/ONFs and endogenous homing stem cells including intrinsic neural progenitor cells and bone marrow stem cells colocalized with specific neural and vascular markers, indicating stem cell fusion. Both hOECs/ONFs and endogenous homing stem cells enhanced neuroplasticity in the rat and mouse ischemic brain. Upregulation of SDF-1alpha and CXCR4 in hOECs/ONFs promoted neurite outgrowth of cocultured primary cortical neurons under oxygen glucose deprivation conditions and in stroke animals through upregulation of cellular prion protein (PrP C) expression. Therefore, the upregulation of SDF-1alpha and the enhancement of CXCR4 and PrP C interaction induced by hOEC/ONF implantation mediated neuroplastic signals in response to hypoxia and ischemia.
authors.affiliation: Center for Neuropsychiatry, China Medical University Hospital, Taichung, Republic of China.
authors.forename: Woei-Cherng
authors.initials: WC
authors.lastname: Shyu
authors.forename: Demeral David
authors.initials: DD
authors.lastname: Liu
authors.forename: Shinn-Zong
authors.initials: SZ
authors.lastname: Lin
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Li
authors.forename: Ching-Yuan
authors.initials: CY
authors.lastname: Su
authors.forename: Ying-Chen
authors.initials: YC
authors.lastname: Chang
authors.forename: Hsiao-Jung
authors.initials: HJ
authors.lastname: Wang
authors.forename: Hsing-Won
authors.initials: HW
authors.lastname: Wang
authors.forename: Chang-Hai
authors.initials: CH
authors.lastname: Tsai
authors.forename: Hung
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D054377:Chemokine CXCL12 / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D005947:Glucose / Q000172:deficiency / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009416:Nerve Regeneration; D016501:Neurites / Q000378:metabolism / Q000502:physiology; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D009473:Neuronal Plasticity / Q000502:physiology*; D009831:Olfactory Mucosa / Q000166:cytology*; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D019718:Receptors, CXCR4 / Q000378:metabolism; D020521:Stroke / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*
chemical_list: D051017:Apoptosis Regulatory Proteins; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D036341:Intercellular Signaling Peptides and Proteins; D018621:PrPC Proteins; D019718:Receptors, CXCR4; D005947:Glucose