Transplantation of Olig2-expressing neural stem cells and adoptive immunotherapy of Myelin basic pro

来源 :中国神经科学学会第九届全国学术会议暨第五届会员代表大会 | 被引量 : 0次 | 上传用户:hjklmijk
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  Neural stem cell transplantation is a major focus of current research in treatment of spinal cord injury (SCI).However, it is very important to promote the transplanted neural stem cells (NSCs) differentiate into OLs and neurons in lesion site.The previous studies have shown that Olig2-overexpression can promote the differentiation of cultured NSCs into mature OLs.Moreover, it has been reported that myelin basic protein activated T cells (MBP-T) can produce neurotrophic factors, improve the SCI local micro-environment, and be neuroprotective to residual myelin and neurons.Therefore, we suppose that combination of Olig2-modified NSC transplantation and MBP-T cell adoptive immunotherapy may have complementary roles in the treatment of SCI.In this study, the MBP-T cells, which can express IFN-γ, IL-10, and IL-13 after activation in vitro, were passively immunized to spinal cord injured rats within one day after SCI.The NSCs, which were infected with lentivirus expressing green fluorescent protein (GFP-NSCs) or Olig2 (Olig2-GFP-NSCs), were transplanted into injured spinal cord 9 d after injury.The fate of transplanted cells was tracked by GFP fluorescence after transplantation in different time points.After adoptive immunotherapy, the transferred MBP-T cells (CD4-positive) could be detected in injured spinal cord from 3 d to 4 w.The infiltration of the MBP-T cells was correlated with and the differentiation of resident microglia and/or infiltrating blood monocytes toward an "alternatively-activated" anti-inflammatory (M2) macrophage phenotype.From 2 to 7 weeks after transplantation, the grafted NSCs could be detected to survive and integrate into the injured spinal cord.At 2 weeks, the survival of grafted NSCs increased fivefold in MBP-T cell-transferred rats compared with vehicle-treated ones.The engrafted GFP-NSCs mostly differentiated into astrocytes, but not OLs and neurons.However, the percentage of MBP-positive OLs increased 12-fold in Olig2-GFP-NSC-engrafted rats compared with GFP-NSC-engrafted ones.Immunofluorescent analyses showed that the grafted Olig2-GFP-NSCs could form central myelin sheaths around the axons in the injured spinal cord.The number of OL-remyelinated axons in animals that received Olig2-GFP-NSC transplantation and MBP-T cell adoptive immunotherapy was significantly increased compared with all other groups.In the MBP-T cells and Olig2-GFP-NSCs combined group, a significant decrease in spinal cord lesion volume along with increase in spared myelin were found compared to the other groups.Such histological improvement correlated well with an increase in behavioral recovery.Thus, combined treatment with Olig2-modified NSC transplantation and MBP-T cell adoptive immunotherapy can enhance remyelination and facilitate functional recovery after traumatic SCI.
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