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Culture And Transplantation Research On Donor Cells For Neural Transplantation

Posted on:2003-04-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:L Y YangFull Text:PDF
GTID:1104360065460486Subject:Neurosurgery
Abstract/Summary:PDF Full Text Request
Current clinical trails suggest that the transplantation of dopaminergic neurons derived from primary human fetal tissues can have beneficial effects in patients with Parkinson's disease,similar trials that involves cell therapy are being undertaken for Huntington's disease and stroke.but this protocol can not be applied to mass patients because human fetal tissues are extremely difficult to abtain in sufficient quantities.three strategies could be selected to resolve this dillema.(l),culture autologous nerve cells(such as neural stem cells) in a patient's CNS and transplant these cells into the same patient,this can prevent the immunological issues.but cells in the CNS is difficult to abtain,and injury was inevitable if this procedure was applied,z>i vitro culture and doubling of these cells have some technical concerns. (2)isolate and culture neural stem cells from embryonic human brains in vitro and transpant these cells into CNS,but this must encounter ethical concerns.(3) another consideration is exogeneic nerve cells(such as pigs),but the safety and immunological rejection are still under investigation, there is a long distance before this cells could be applied to clinics.for example,transplantation procedure encounter the danger of transferring pathogens in animals to human bodies.cell sources mentioned above all have some shortcomings,it is necessary to consult other sources.Neural stem cells become the reseach focus of neurobiology in the recent years,it is possible that they could be cell sources for CNS transplantation.Parkinson's and transient ischemic rats have been relieved by NSCs transplantation,recent report release the news that Okano professor in Keio University have cured primates suffered from spinal cord injuries,motor disorders have achieved apparent improvement.we have successfully cultured human neural stem cells(NSCs) from embryonic brains,they expressed Musashil and vimentin,and could differentiate into neurons,astrocytes and oligodendrocytes,and we also observed myelin formation in the floating neurospheres.cells implanted into the cerebral ventricles of embryonic rats incorporate individually into all major compartments of the brains,generatingwidespread chimerism.developing cues guide transplanted human cells to migrate towards definite directions,and this implies remarkable conservation of these signals across species.Human tissues such as bone marrow,skin and adipose are easily accessible.if stem cells from these tissues could be cultured and expanded in vitro,nerve cells could be differentated from these cells,this would provide enough cells for CNS transplantation,and give convenience for logistic and ethical concerns and circumvent the use of human fetus.the existence of stem cells for nonhematopoietic cells in bone marrow was proposed over 100 years ago,but the isolation and differentiation of marrow stromal cells into osteoblasts,adipocytes,and myoblasts was only recentlydemonstrated.nonhematopoietic precursors from bone marrow stroma have been refered to as colony-forming-unit fibroblasts,mesenchymal stem cells,or bone marrow stromal cells(BMSCs), here we called it BMSCs.recent studies have demonstrated that BMSCs could be differentaited into neurons in vivo and in vz/ro,we have adapted similar protocol to induce BMSCs into neuron-like cells,the differentiating cells expressed nestin and Musashil at the early stage of differentiation,terminal differntiated cells expressed NSE and NF-M. We have demonstrated the effect of salvia miltiorrhiza on neuronal differentiation of BMSCs.cells migrated some distance in the adult rat brains when they were transplanted into striatum,no obvious local proliferation , gliosis and lymphocyte infiltration were observed,transplanted cells showed good compatibility with the host brains.All of above indicated that BMSCs could differentiate into neurons,they may be potential sources for CNS cell transplantation.Adipose tissue-derived stromal cell(ADMCs) share some simularities with BMSCs:(l)they are both derived from mesoderm;(2)th...
Keywords/Search Tags:neuron, differentiation, neural stem cell/neural progenitor/neural precursor, astrocyte, oligodendrocyte, bone marrow stromal cell, adipose, adipocyte, adipose tissue-derived stromal cell, osteogenic cell, skin-derived precursor, cell transplantation
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