The Treatment Of Parkinson's Disease (PD) Model Of Rhesus Monkey With Self-Transplantation Of NSCs-BMSCs (Neural Stem Cells Derived From Bone Marrow Stromal Cells) Modified With Tyroxine Hydroxylase (TH) Gene

Parkinson's disease (PD) is firstly described in 1817 by James Parkinson, an English physician, as a neurodegenerative disease characterised by a progressive loss of the dopaminergic neurones in the substantia nigra pars compacta, Accumulating evidence indicates that apoptosis contributes to neuronal cell death in PD patients' brain. Excitotoxicity, oxidative stress, and mitochondrial respiratory failure are thought to be the key inducers of the apoptotic cascade. Even though the initial cause and the mechanism of degeneration are poorly understood,Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects approximately 1,000,000 Americans. The histopathological hallmarks of the disease are dopaminergic striatal insufficiency secondary to a loss of dopaminergic neurons in the substantia nigra pars compacta and intracellular inclusion called Lewy bodies. Currently, Although some treatments are efficacious for many years, all have significant limitations, such as only symptomatic treatment for PD, but unable to prevent the progress of PD , and new therapeutic approaches are needed. Gene therapy is ideal for delivering therapeutic molecules to site-specific regions of the central nervous system. Via gene therapy, a piece or pieces of DNAplaced into a carrying vector encoding for a substance of interest can be introduced into specific cells. With the development of neural stem cells (NSCs), molecular cloning and gene recombination technology, gene therapy for PD with NSCs has a cheerful prospect.At present, there are two main ways that gene therapy can be applied for PD. One way focuses on in vivo or in vitro gene delivery of tyrosine hydroxylase (TH) , a key enzyme in the pathway, to make neuronal cells more efficiently convert L-dopa into dopamine to relieve the symptom of PD, or potential agents for neuroprotection, neurotrophic factors, inhibitors of apoptosis or anti-oxidative agents as neuroprotective strategy for PD, to achieve neuroprotection by interfering with neuronal cell death either directly or by preventing neuronal dysfunction. Another way isinclined to co-transfect with cDNAs coding for catecholamine-synthesizing genes and neurotrophic factors genes such as glial cell line-derived neurotrophic factors to attain neurotransmitter replacement therapy.In vivo gene delivery is a technology with injecting therapeusis gene into target site as the biologic drug pump to produce neurotransmitter. The method is characteristics of direction and convenience, but lower transfection efficiency and gene expression, and can not screen and evaluate before gene delivery in vivo. Ex vivo gene delivery could furthermore be combined with cell replacement therapies by transplanting genetically modified cells compensating for the lost neuronal cell population in order to provide neuroprotection to both the grafted cells and degenerating host neurones. However, several aspects of gene transfer, such as uncontrolled diffusion, axonal transport, unpredictable site of integration and immunological responses, still raise safety concerns and justify further development of viral and non-viral vectors as well as genetic elements with tightly controlled gene expression. Various relevant animal models for Parkinson's disease areavailable for the evaluation of gene therapy strategies.There are some kind s of cells considered as target cells of gene therapy for Parkinson's disease, such as Fibroblast, skeletal muscle cells, glial cell, embryo mesencephalon cell, neural stem cell. Meanwhile, recombination fibroblast and skeletal muscle cells can easily be cultivated to transplant to achieve some curative effect, but they could not be alive for a long time and not relate to host cells with synapse in brain. In addition, embryo mesencephalon cell and embryo neural stem cell and adult neural stem cell exists in some problem of limited source and heterology to restrict their clinic application in gene therapy for Parkinson's disease. Nevertheless, Bone marrow (BM) contains hematopoietic stem cells (HS...