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The Empirical Study On The Repair Of Spinal Cord Injury By Transplantation Of Autogeneic Mesenchymal Stem Cells And Electro-stimulant Therapy

Posted on:2009-06-26Degree:MasterType:Thesis
Country:ChinaCandidate:B XieFull Text:PDF
GTID:2144360245496240Subject:Surgery
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The spinal cord injury(SCI)can lead to severe and permanent neurological deficits.Although no effective therapeutic option is currently available,recent animal studies have shown that cellular transplantation strategies hold promise to enhance functional recovery after spinal cord injury(SCI).There are many kinds of cells which can be used for transplantation, such as mesenchymal stem cells(MSCs)who have the potency to differentiate into a variety of cell types,including bone,cartilage,muscle, glia,and neurons.Compared with other kinds of cells,MSCs have several advantages,in that they are relatively easy to isolate from the patient's own bone marrow,the lack of ethical controversy regarding their derivation,avoiding any risk of rejection or the considerable sideeffects associated with immunosuppression,without creating any further CNS damage;they can then be expanded in vitro to increase numbers; moreover,the fact that they have been used for many years in the treatment ofhaematopoietic diseases means that protocols regarding isolation,application and safety are well established.A number of studies indicate that these cells can be derived to various tissues and thus exhibit slightly differing final properties,especially,more recent evidence suggests that MSCs can indeed differentiate into neurotransmitter responsive cells with the electrophysiological properties ofneurones at least,and they also release neurotrophic factors,which can promote the recovery of impaired medullary sheath and survival nerve fiber.Electric stimulation was not main therapy method in the study of regeneration of nerve tissue,but more and more evidence certified that the effect of facilitating nerve tissue regeneration was underestimated. The experimentation has shown t hat applied pulse electric fields:(a) induced microcurrent which direction was contra with endogeny injury current after SCI,and mitigated the endogenous injury after SCI;(b) advanced various kinds enzyme reactiveness of nerve cell,advanced transportation ability of axon,metabolism productive,profit for regeneration;(c)changed functional status of nerve cell,influenced the excitability of nerve cell by regulated content of glycine.(d)induced neurites to grow toward the negative pole(cathode)of the applied voltage gradient through sometimes remarkable trajectories.Quibus,we designed this experiment,combined the transplantation of MSCs with electro-stimulant to treat the spinal cord injury,and check that if we can get a prefer therapeutic efficacy.We evaluated the therapeutic efficacy by BBB scores,SEP,immunohistochemistry and MRI.Objective:To evaluate the effects of transplantation of autogeneic mesenchymal stem cells(MSCs)with electro-stimulant therapy after spinal cord injury(SCI).Methods:In this study,60 male Wistar rats were used.A digital weight drop apparatus induced spinal cord lesion was performed to mimic human SCI.Seven days after SCI,we collected and labeled the MSCs from each rat's femurs.The rats were randomly assigned into four groups. The first group(A group)(n15)received a transplation of MSCs only, the second group(B group)(n15)received electro-stimulant therapy only,while the third group(C group)(n15)received a transplation of MSCs and electro-stimulant therapy,The control group(D group)(n 15) received a single injection of phosphate buffer solution(PBS)after SCI. Functional status was assessed before SCI and weekly after SCI,using the Basso-Beattie-Bresnehan(BBB)locomotor rating score and somatosensory evoked potential(SEP),then observe the survivorship of MSCs using Bromodeoxyuridine(Brdu),and check the recovery of spinal cord by MRI three diamensions images and DTI images.Results:BBB score was higher in research group than that in the control group.Statistical differences showed in inter-group after 4 weeks(P<0.05).Statistical differences showed in latency period and wave amplitude in SEP after 7 and 8 weeks(P<0.05).Histology confirmed a large number of Bromodeoxyuridine(Brdu)-positive cells in the lesion site.MR images of the spinal cords 7,8 weeks after transplantation by made restitution of three diamensions and DTI showed the recovery of spinal cord lesion.Conclusion:We conclude that treatment with three different methods have a positive effect on behavioral outcome and histopathological assessment after SCI,which was most pronounced after MSCs trasplation and electro-stimulant therapy.
Keywords/Search Tags:autogeneic, mesenchymal stem cells, electro-stimulant, repair
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