Lu Zheng-qi, Hu Xue-qiang, Zhu Can-sheng, Zheng Xue-ping, Wan Dun-jing, Liu Ran-yi, Huang Bi-jun, Huang Wen-lin
Department of Neurology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2009 Dec;29(12):2355-61.
To investigate the anti-inflammatory effect of bone marrow stromal cells (MSCs) transfected with recombinant adenovirus-mediated ciliary neurotrophic factor (CNTF) gene in C57BL/6 mice with experimental allergic encephalomyelitis (EAE).
An adenovirus vector containing CNTF gene Ad-CNTF-IRES-GFP was constructed and transfected in the MSCs (MSC-CNTF). After examination of CNTF expression, the transfected cells were transplanted in C57BL/6 mice with MOG 35-55-induced EAE, which were monitored for the changes in the symptoms scores. The levels of tumor necrosis factor-alpha (TNF-alpha), inteferon-gamma (IFN-gamma), interleukin-12P35 (IL-12P35), and IL-10 in the peripheral blood of the mice were detected, and the number of MSC-CNTF cells in the spleen and spinal cord was counted. CD3+ T cell infiltration and TNF-alpha and IFN-gamma expressions in the lesions were also observed after the cell transplantation.
CNTF gene transfection resulted in significantly increased CNTF expression in the MSCs. The mice receiving MSC-CNTF transplantation exhibited significantly improved symptoms with shortened disease course and lessened disease severity. The cell transplantation also resulted in significantly decreased peripheral blood TNF-alpha levels, ameliorated CD3+T cell infiltrations and lowered TNF-alpha expression in the lesions, while the levels of IFN-gamma underwent no significant changes.
Transplantation of CNTF gene-transfected MSCs results in decreased peripheral blood TNF-alpha and IFN-gamma levels and reduced inflammatory cells, CD3-positive cells and TNF-alpha expression in the lesion of EAE, therefore providing better effect than MSCs in relieving the symptoms of EAE in mice.
研究重组腺病毒介导的睫状神经营养因子(CNTF)基因转染的骨髓基质细胞(MSCs)对实验性自身免疫性脑脊髓炎(EAE)C57BL/6小鼠的抗炎作用。
构建含CNTF基因的腺病毒载体Ad-CNTF-IRES-GFP并转染至MSCs(MSC-CNTF)。检测CNTF表达后,将转染细胞移植到经髓鞘少突胶质细胞糖蛋白35-55(MOG 35-55)诱导的EAE C57BL/6小鼠中,监测症状评分变化。检测小鼠外周血中肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)、白细胞介素-12P35(IL-12P35)和IL-10水平,并计数脾脏和脊髓中MSC-CNTF细胞数量。细胞移植后还观察了病变部位CD3+ T细胞浸润及TNF-α和IFN-γ表达情况。
CNTF基因转染使MSCs中CNTF表达显著增加。接受MSC-CNTF移植的小鼠症状明显改善,病程缩短,疾病严重程度减轻。细胞移植还使外周血TNF-α水平显著降低,改善了CD3+ T细胞浸润,降低了病变部位TNF-α表达,而IFN-γ水平无明显变化。
移植CNTF基因转染的MSCs可降低外周血TNF-α和IFN-γ水平,减少EAE病变部位炎症细胞、CD3阳性细胞及TNF-α表达,因此在缓解小鼠EAE症状方面比MSCs效果更好。