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

被引：96

作者：

Shyu, Woei-Cherng ^{[2
,3
]}

Liu, Demeral David ^{[1
]}

Lin, Shinn-Zong ^{[2
,3
]}

Li, Wen-Wen ^{[4
]}

Su, Ching-Yuan ^{[5
]}

Chang, Ying-Chen ^{[2
,3
]}

Wang, Hsiao-Jung ^{[2
,3
]}

Wang, Hsing-Won ^{[6
]}

Tsai, Chang-Hai ^{[7
]}

Li, Hung ^{[4
,5
]}

机构：

[1] China Med Univ Hosp, Dept Dent, Taichung 40447, Taiwan

[2] China Med Univ Hosp, Ctr Neuropsychiat, Taichung 40447, Taiwan

[3] Buddhist Tzu Chi Gen Hosp, Hualien 970, Taiwan

[4] Natl Yang Ming Univ, Inst Biochem & Mol Biol, Taipei 112, Taiwan

[5] Acad Sinica, Inst Mol Biol, Taipei, Taiwan

[6] Tri Serv Gen Hosp, Dept ENT, Natl Def Med Ctr, Taipei, Taiwan

[7] China Med Univ Hosp, Dept Med Res, Taichung 40447, Taiwan

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2008年 / 118卷 / 07期

关键词：

D O I：

10.1172/JCI34363

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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-l alpha (SDF-1 alpha). Rats with intracerebral hOEC/ONF implantation showed more improvement on behavioral measures of neurological deficit following stroke than control rats. [F-18]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-1 alpha 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-1 alpha and the enhancement of CXCR4 and PrPC interaction induced by hOEC/ONF implantation mediated neuroplastic signals in response to hypoxia and ischemia.

引用

页码：2482 / 2495

页数：14

共 88 条

[1] Olfactory ensheathing cell transplantation restores functional deficits in rat model of Parkinson's disease: a cotransplantation approach with fetal ventral mesencephalic cells [J].