The therapeutic effects of tyrosine hydroxylase gene transfected hematopoetic stem cells in a rat model of Parkinson's disease.
OBJECTIVE
To investigate the therapeutic effects of tyrosine hydroxylase (TH)-transfected neuronal stem cells derived from bone marrow stem cells (NdSCs-D-BMSCs) on Parkinson's disease (PD) through different transplantation protocols, including microinjection into the cerebral ventricles (CV) and the striatum (ST).


METHODS
After identification by enzyme digestion, the constructed plasmid pEGFP-C2-TH was transfected into 8-day-cultured NdSCs-D-BMSCs by electroporation resulting in the coexpression of green fluorescent protein (GFP) and TH. The TH-transfected cells were injected into either the right ST or CV of PD rats. The changes in locomotor activity of PD rats and the migration of transplanted cells in cerebral tissue were monitored and cerebral DA levels were assayed by high performance liquid chromatography (HPLC).


RESULTS
Five days after plasmid pEGFP-C2-TH transfection into NdSCs-D-BMSCs GFP was expressed in 62.1% of the cells and the rate of co-expression with TH was 83.5%. Ten weeks following transplantation, the symptoms of PD rats in both groups were significantly improved and DA levels were restored to 46.6% and 33% of control. The transferred cells showed excellent survival rates in PD rat brains and distant migration was observed.


CONCLUSIONS
Both CV and ST transplantation of TH-transfected NDSCs-D-BMSCs has obvious therapeutic effects on PD rats. This study could provide evidence for future transplantation route selection, possibly leading to stem cell transplantation through lumbar puncture.
Zhang
Shizhong
S
Neuromedical Institute, Zhujiang Hospital, South Medical University, Guangzhou City 510282, PR China. shizhongzh@hotmail.com
Zou
Zhihao
Z
Jiang
Xiaodan
X
Xu
Ruxiang
R
Zhang
Wangming
W
Zhou
Yuan
Y
Ke
Yiquan
Y
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000379:methods; D002454:Cell Differentiation; D002478:Cells, Cultured; D003342:Corpus Striatum; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D009474:Neurons / Q000502:physiology; D010300:Parkinson Disease / Q000235:genetics / Q000628:therapy*; D010957:Plasmids / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014162:Transfection; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics* / Q000378:metabolism
D014446:Tyrosine 3-Monooxygenase
J Neurosci Res. 2000 Aug 15;61(4):364-70
10931522
Am J Pharmacogenomics. 2002;2(2):135-46
12083948
Exp Neurol. 2005 Jun;193(2):444-54
15869947
Brain Res Brain Res Protoc. 2005 May;15(1):46-51
15878150
Nature. 1998 Apr 9;392(6676):605-8
9560156
Hum Cell. 2001 Mar;14(1):39-48
11436352
Ann Neurol. 2003 Sep;54(3):352-9
12953267
J Neurosci Methods. 2005 May 15;144(1):35-45
15848237
Leuk Lymphoma. 2002 Dec;43(12):2263-8
12613511
Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):7841-5
11427725
Neurotoxicology. 2005 Oct;26(5):869-81
15890406