Modo Michel, Rezaie Payam, Heuschling Paul, Patel Sara, Male David K, Hodges Helen
Neuroimaging Research Group-Neurology P042, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK.
Brain Res. 2002 Dec 20;958(1):70-82. doi: 10.1016/s0006-8993(02)03463-7.
The use of progenitors and stem cells for neural grafting is promising, as these not only have the potential to be maintained in vitro until use, but may also prove less likely to evoke an immunogenic response in the host, when compared to primary (fetal) grafts. We investigated whether the short-term survival of a grafted conditionally immortalised murine neuroepithelial stem cell line (MHP36) (2 weeks post-implantation, 4 weeks post-ischaemia) is influenced by: (i) immunosuppression (cyclosporin A (CSA) vs. no CSA), (ii) the local (intact vs. lesioned hemisphere), or (iii) global (lesioned vs. sham) brain environment. MHP36 cells were transplanted ipsi- and contralateral to the lesion in rats with middle cerebral artery occlusion (MCAo) or sham controls. Animals were either administered CSA or received no immunosuppressive treatment. A proliferation assay of lymphocytes dissociated from cervical lymph nodes, grading of the survival of the grafted cells, and histological evaluation of the immune response revealed no significant difference between animals treated with or without CSA. There was no difference in survival or immunological response to cells grafted ipsi- or contralateral to the lesion. Although a local upregulation of immunological markers (MHC class I, MHC class II, CD45, CD11b) was detected around the injection site and the ischaemic lesion, these were not specifically upregulated in response to transplanted cells. These results provide evidence for the low immunogenic properties of MHP36 cells during the initial period following implantation, known to be associated with an acute host immune response and ensuing graft rejection.
将祖细胞和干细胞用于神经移植很有前景,因为这些细胞不仅有可能在体外维持到使用时,而且与原代(胎儿)移植相比,在宿主体内引发免疫原性反应的可能性可能更小。我们研究了移植的条件永生化小鼠神经上皮干细胞系(MHP36)(植入后2周,缺血后4周)的短期存活是否受以下因素影响:(i)免疫抑制(环孢素A(CSA)与无CSA),(ii)局部(完整半球与损伤半球),或(iii)整体(损伤脑与假手术脑)脑环境。将MHP36细胞移植到大脑中动脉闭塞(MCAo)大鼠或假手术对照组的损伤同侧和对侧。动物要么接受CSA治疗,要么不接受免疫抑制治疗。对从颈淋巴结分离的淋巴细胞进行增殖测定、对移植细胞的存活进行分级以及对免疫反应进行组织学评估,结果显示接受或未接受CSA治疗的动物之间没有显著差异。移植到损伤同侧或对侧的细胞在存活或免疫反应方面没有差异。尽管在注射部位和缺血损伤周围检测到免疫标记物(MHC I类、MHC II类、CD45、CD11b)的局部上调,但这些标记物并非因移植细胞而特异性上调。这些结果为MHP36细胞在植入后的初始阶段具有低免疫原性提供了证据,已知该阶段与急性宿主免疫反应及随后的移植排斥有关。