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

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

Research output: Contribution to journalArticle

80 Citations (Scopus)

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

Original languageEnglish
Pages (from-to)2482-2495
Number of pages14
JournalJournal of Clinical Investigation
Volume118
Issue number7
DOIs
Publication statusPublished - Jul 1 2008
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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