Therapeutic benefit of TH-engineered mesenchymal stem cells for Parkinson's disease.
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.
Lu
Lingling
L
Beijing Institute for Neuroscience, The Beijing Center of Neural Regeneration and Repairing, Capital University of Medical Sciences, 10# You'anMen Wai Xitoutiao, Beijing 100054, P.R. China.
Zhao
Chunli
C
Liu
Yujun
Y
Sun
Xiaohong
X
Duan
Chunli
C
Ji
Man
M
Zhao
Huanying
H
Xu
Qunyuan
Q
Yang
Hui
H
D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D000229:Dependovirus / Q000235:genetics; D004298:Dopamine / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D017072:Neostriatum / Q000201:enzymology / Q000378:metabolism; D016627:Oxidopamine; D010300:Parkinson Disease / Q000628:therapy*; D010957:Plasmids / Q000235:genetics; D015202:Protein Engineering; D051381:Rats; D017207:Rats, Sprague-Dawley; D013565:Sympatholytics; D014162:Transfection; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D013565:Sympatholytics; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine