Implantation of olfactory ensheathing cells promotes neuroplasticity in murine models of stroke.
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.
Shyu
Woei-Cherng
WC
Center for Neuropsychiatry, China Medical University Hospital, Taichung, Republic of China.
Liu
Demeral David
DD
Lin
Shinn-Zong
SZ
Li
Wen-Wen
WW
Su
Ching-Yuan
CY
Chang
Ying-Chen
YC
Wang
Hsiao-Jung
HJ
Wang
Hsing-Won
HW
Tsai
Chang-Hai
CH
Li
Hung
H
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*
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