| Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the midbrain and, consequently, depletion of dopamine in the striatum. Considering the growing number of the elderly, it has become an increasing burden for both the society and the family. Up to now, it has not been known what factors and mechanisms can decipher the reasons of PD. It seems that environmental and genetic factors play some important roles during the procedure. However, the pathological and biochemical changes, i.e. dopaminergic neurons death and dopamine decrease, have been deeply investigated and clearly described. Dysfunction of this neurotransmitter results in clinical symptoms including rigidity, resting tremor, bradykinesia and so on. For a long time, people wants to find out an effective method to cure Parkinson' disease. Due to the characterized pathological changes, it is possible to treat the disease when cells that can synthesize and secrete dopamine are intracerebrally transplanted. Bone marrow mesenchymal stem cells (MSCs) are multipotent tissue stem cells that can beinduced in vitro to differentiate into mesenchymal and non-mesenchymal cells. MSCs can differentiate into osteoblasts, chondrocytes, adipocytes, and hepatocytes. It has also been suggested that they might be able to differentiate into other phenotypes as well, including neuronal cells. Brain derived neurotrophic factor (BDNF) is one of the neurotrophic factors family, is reported to be produced by MSCs, and promotes the survival and differentiation of neuronal tissue. Therefore, MSCs are excellent seed cells for treating nervous system diseases, damages, genetic defects and degeneration diseases. Here, we examined the isolation, purification and expansion of human bone marrow MSCs in vitro. After transduction of brain-derived neurotrophic factor (BDNF) gene via recombinant retroviral vectors into the human MSCs, nearly 100% of cells expressed BDNF (which were therefore transformed into BNDF-MSCs) as detected by immunocytochemistry, and the quantity of BDNF in the culture medium was increased by approximately 20 000 fold. In spite of the genomic integration of an exogenous gene, BDNF-MSCs did not present any structural aberration in the chromosomes. When BDNF-MSCs were injected into the striatum of Parkinson's disease model rats, and examined their survival, migration, differentiation and the behavior change of PD rats, which will provide theoretical foundation and technical method for clinic PD therapy by stem cells. The results showed that human bone marrow MSCs can survive in rat brain for a longer while (exceeding 90d). Some cells with endothelium-like phenotype were localized in blood vessel wall, which is perhaps correlated to tissue repair. Immunocytochemical staining suggested that implanted cells expressed human NF, NSE and glial fibrillary acid protein (GFAP). Behavioral deficits in PD rats were more ameliorated by the transplantation of BDNF-MSCs than the transplantation of MSCs. It revealed that BDNF Gene-modified human bone marrow MSCs can play a role under rat brain microenvirment and could become seed cells for treating PD.Conclusions:l.We established a kind of method to isolate and to purificate MSCs,the method was simple and executable,we could set up a standard criterion by the method,and made a technical platform for evluating MSCs.2.The biological characteristics of MSCs were in part estimated by analysing the surface antigenes of MSCs in flow cytometry.3.After transduction of brain-derived neurotrophic factor gene via recombinant retro-viral vectors into the human MSCs, it was established that the BDNF-MSCs finite cell line.4.The PD model rats were made by injection 6-OHDA into the rat brains. 5.The human marrow MSCs were transplantated in PD model rat brains,provided a new way to recruit PD. |
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