Therapeutic benefit of TH-engineered mesenchymal stem cells for Parkinson's disease

被引：107

作者：

Lu, LL ^{[1
]}

Zhao, CL ^{[1
]}

Liu, YJ ^{[1
]}

Sun, XH ^{[1
]}

Duan, CL ^{[1
]}

Ji, M ^{[1
]}

Zhao, HY ^{[1
]}

Xu, QY ^{[1
]}

Yang, H ^{[1
]}

机构：

[1] Capital Univ Med Sci, Beijing Ctr Neural Regenerat & Repairing, Beijing Inst Neurosci, Beijing 100054, Peoples R China

来源：

BRAIN RESEARCH PROTOCOLS | 2005年 / 15卷 / 01期

关键词：

mesenchymal stein cells; TH gene; Parkinson's disease; AAV; gene transfection;

D O I：

10.1016/j.brainresprot.2005.03.002

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

The present study was designed to assess the potential of marrow stromal cells (MSCs) to deliver therapeutic genes to the brain and result in biologically significant functional recovery. The tyrosine hydroxylase (TH) gene was transfected to MSCs with an adeno-associated virus (AAV) vector. MSCs expressing TH gene were transplanted into the striatum of Parkinson's disease (PD) rat. The asymmetric rotation of these models after apomorphine administration was detected every week after transplantation. Six weeks after grafting, animals were sacrificed. Some brains were sectioned to do TH immunohistochemistry. The others were used to detect the dopamine levels by high-performance liquid chromatograph and electrochemical detection (HPLC-ECD). The results showed that MSCs multiply rapidly and formed fibroblast colony-forming units in primary culture. The gene expression efficiency was about 75%. The rounds of asymmetric rotation after apomorphine administration decreased after TH-engineered MSCs were grafted. Histological examination showed that TH gene was expressed around the transplantation points. The dopamine level in the lesioned striatum of rats injected with TH-MSCs was significantly greater than that in rats treated with LacZ-MSCs (P < 0.05). All the data demonstrated that MSCs could readily be genetically engineered. Therefore, MSCs could be useful gene delivery vehicles of gene therapy for Parkinson's disease. (c) 2005 Elsevier B.V. All rights reserved.

引用

页码：46 / 51

页数：6

共 28 条

[1] Engraftment and migration of human bone marrow stromal cells implanted in the brains of albino rats - similarities to astrocyte grafts [J].