[Show abstract][Hide abstract] ABSTRACT: In the present study, to establish a stromal cell derived factor-1α α α α (SDF-1α α α α) mouse Parkinson's disease (PD) model, low-dose 1-methyl-4-phenyl-tet-rahy dropyridine (MPTP) was subcutaneously injected at different time points into mice which had been intracerebrally treated with pDsRed2-N1-SDF-1α α α α, and behaviors were observed at different time points. The pod-grabbing time, the number of tyrosine hydroxylase (TH) positive cells and the expression of SDF-1α α α α in the brain were determined at different time points. PD-like behaviors were observed in the mice of MPTP group and could last for at least 40 days. At different time points, the pod-grabbing time in MPTP group was longer than that in control group, but the TH positive cells and DA content were markedly decreased when compared with control group. In addition, plasmid transcription was noted in MPTP group and SDF-1α α α α expression was detectable. Intermittent and multiple subcutaneous injections of MPTP can be used to establish a PD model in SDF-1α α α α over-expressing mice, which provides an experimental basis for the investigation of the role of SDF-1α α α α induced chemotaxis and migration in the treatment of PD.
Scientific research and essays 02/2011; 6(4). · 0.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mesenchymal stem cells are capable of differentiating into dopaminergic-like cells, but currently no report has been available to describe the induction of human umbilical vein mesenchymal stem cells (HUVMSCs) into dopaminergic-like cells. In this study, we induced HUVMSCs in vitro into neurospheres constituted by neural stem-like cells, and further into cells bearing strong morphological, phenotypic and functional resemblances with dopaminergic-like cells. These HUVMSC-derived dopaminergic-like cells, after grafting into the brain of a rat model of Parkinson's disease (PD), showed a partial therapeutic effect in terms of the behavioral improvement. Nerve growth factor was reported to improve the local microenvironment of the grafted cells, and we therefore further tested the effect of dopaminergic-like cell grafting combined with nerve growth factor (NGF) administration at the site of cell transplantation. The results showed that NGF administration significantly promoted the survival of the grafted cells in the host brain and enhanced the content of dopaminergic in the local brain tissue. Behavioral test demonstrated a significant improvement of the motor function of the PD rats after dopaminergic-like cell grafting with NGF administration as compared with that of rats receiving the cell grafting only. These results suggest that transplantation of the dopaminergic-like cells combined with NGF administration may represent a new strategy of stem cell therapy for PD.
Neurochemical Research 10/2010; 35(10):1522-9. DOI:10.1007/s11064-010-0211-6 · 2.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Brain research 07/2010; 1346:279-86. DOI:10.1016/j.brainres.2010.05.071 · 2.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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).
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).
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.
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.