Efficacy of Tyrosine Hydroxylase gene modified neural stem cells derived from bone marrow on Parkinson's disease--a rat model study.
The aim of this study is to determine the efficacy of injecting adult bone marrow derived stem cells (BMSCs) transfected with a pEGFP-C2 plasmid containing the gene for Tyrosine Hydroxylase (TH) into the lateral ventricle for treating rats with Parkinson's Disease (PD) induced by injections into the Substantia Nigra pars compacta (SNc) with 6-hydroxydopamine (6-OHDA), a potent and selective neurotoxin for catecholamine expressing neurons. BMSCs were obtained from the femur of rats; transfected with plasmid constructed with TH and green fluorescent protein (GFP) (with about 85% co-transfection efficiency rate) and then cultured with neuronal differentiation media. Eighty rats were injected into the SNc with 6-OHDA and tested behaviorally to verify the model was induced. Then, 12 PD rats were injected into the anterior horn of the lateral ventricle with x10(5) cells, while 12 more rats were given saline as control. We found that 10 days after transplantation there was a significant (P<0.01) reduction in Apomorphine induced rotations in rats receiving transplanted cells. Also, combined SNc and Striatal dopamine contents (microg/g wet tissue weight) in transplanted rats were greater than controls (0.19+/-0.06 vs 0.63+/-0.14 P<0.01). Immunohistological examination found GFP expression, indicating the presence of transplanted cells within the brain, some of which had migrated through the nerve fibers along the ventricular wall. We feel this study shows the efficacy of genetically engineered BMSCs in the treatment of a rat model of PD. However, future experiments are needed to determine the mechanisms.
Zou
Zhihao
Z
Neuromedical Institute, Zhujiang Hospital, South Medical University, Guangzhou City, 510282, P.R. China. zouzh1976@163.com
Jiang
Xiaodan
X
Zhang
Wangming
W
Zhou
Yuan
Y
Ke
Yiquan
Y
Zhang
Shizhong
S
Xu
Ruxiang
R
D000818:Animals; D001522:Behavior, Animal; D016026:Bone Marrow Transplantation; D001923:Brain Chemistry / Q000502:physiology; D002454:Cell Differentiation; D004298:Dopamine / Q000378:metabolism; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D007276:Injections, Intraventricular; D020547:Lateral Ventricles / Q000166:cytology; D008297:Male; D009474:Neurons / Q000201:enzymology* / Q000637:transplantation*; D020258:Neurotoxicity Syndromes / Q000628:therapy; D016627:Oxidopamine / Q000008:administration & dosage; D010300:Parkinson Disease / Q000628:therapy*; D010957:Plasmids / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000201:enzymology*; D013565:Sympatholytics / Q000008:administration & dosage; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D013565:Sympatholytics; D049452:Green Fluorescent Proteins; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine