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Implantation of olfactory ensheathing cells promotes neuroplasticity in murine models of stroke
Woei-Cherng Shyu, … , Chang-Hai Tsai, Hung Li
Woei-Cherng Shyu, … , Chang-Hai Tsai, Hung Li
Published June 5, 2008
Citation Information: J Clin Invest. 2008;118(7):2482-2495. https://doi.org/10.1172/JCI34363.
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Research Article Neuroscience

Implantation of olfactory ensheathing cells promotes neuroplasticity in murine models of stroke

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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–1α (SDF-1α). 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-1α 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 (PrPC) expression. Therefore, the upregulation of SDF-1α and the enhancement of CXCR4 and PrPC interaction induced by hOEC/ONF implantation mediated neuroplastic signals in response to hypoxia and ischemia.

Authors

Woei-Cherng Shyu, Demeral David Liu, Shinn-Zong Lin, Wen-Wen Li, Ching-Yuan Su, Ying-Chen Chang, Hsiao-Jung Wang, Hsing-Won Wang, Chang-Hai Tsai, Hung Li

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Figure 6

Biological mechanism of neuroplastic effects on the ischemic brain after intracerebral transplantation of hOECs/ONFs.

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Biological mechanism of neuroplastic effects on the ischemic brain after...
(A) In a representative brain section of a GFP-chimeric mouse treated with or without hOECs/ONFs (white arrow indicates the injection site), GFP+ cells are seen dispersed over the periphery of the transplanted hOECs/ONFs and were significantly increased in quantity in the hOEC/ONF-treated mice in comparison with controls. In FISH analysis (white arrow, 2 red spots), hOECs/ONFs were shown to be of human origin (inset square in left panel). (B) IHC of hOEC/ONF treatment in the BrdU-labeled mice. Many BrdU+nestin+ cells were distributed around the transplanted hOECs/ONFs. (C) Interestingly, 1 cell with 2 nuclei (cell fusion) was found in the implanted hOECs/ONFs (white arrows, blue nucleus) and GFP+ cells (white arrowheads, red nucleus). The nucleic dye TOTO-3 (red) was used to define the outline of all nuclei in the section. (D) In a colocalization study (3D image) some bis-benzimide–labeled cells and some GFP+ cells colocalized with MAP-2+, vWF+, and GFAP+ cells in the penumbra of hOEC/ONF-treated ischemic rat brains. (E) SDF-1α–immunoreactive cells colocalized with a few bis-benzimide–labeled hOECs/ONFs and GFP+ cells. Data are expressed as mean ± SEM. *P < 0.05 versus control. Scale bars: 50 μm.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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