Immunogenicity of allogeneic adipose-derived stem cells in a rat spinal fusion model.
Immunogenicity of allogeneic adipose-derived stem cells in a rat spinal fusion model.
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DOI：
10.1089/ten.tea.2008.0566
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发表时间：
2009-09
影响因子：
--
通讯作者：
Gimble JM
中科院分区：
文献类型：
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作者：
McIntosh KR;Lopez MJ;Borneman JN;Spencer ND;Anderson PA;Gimble JM
脂肪源性干细胞（ASC）表达非免疫原性特征，如体外研究所示，该研究表明缺乏T细胞向同种异体ASC的增殖以及ASC介导的混合淋巴细胞反应抑制。为了确定这些观察结果是否会在体内转化，结合大鼠脊柱融合研究进行了免疫监测研究。将来源于Fischer或ACI品系大鼠的ASC加载到支架上并植入已经经历以下处理的Fischer受体中：（1）未处理;（2）仅支架;（3）同基因ASC+支架;或（4）同种异体ASC+支架。在植入后4周处死每组的一半动物，在8周处死剩余动物。如在单独的研究中所确定的，与无处理组和仅支架对照组相比，同种异体和同基因ASC在加速脊柱融合方面同样有效。为了确定供体ASC是否在受体大鼠中诱导免疫应答，收获淋巴结用于T细胞增殖研究，并收集血清以评估抗体应答。尽管在任一时间点均未检测到受体中对供体同种抗原的T细胞引发，但在植入同基因或同种异体ASC的动物中检测到对ACI ASC的显著抗体应答。抗体为IgG同种型，在补体存在下无细胞毒性，对胎牛血清有反应。这些结果支持同种异体ASC用于脊柱融合。
Adipose-derived stem cells (ASCs) express a nonimmunogenic profile as shown by in vitro studies that demonstrate a lack of T cell proliferation to allogeneic ASCs as well as ASC-mediated suppression of mixed lymphocyte reactions. To determine whether these observations would translate in vivo, immune monitoring studies were carried out in conjunction with a rat spinal fusion study. ASCs derived from Fischer or ACI strain rats were loaded onto scaffolds and implanted in Fischer recipients that had undergone the following treatments: (1) No treatment; (2) Scaffold only; (3) Syngeneic ASCs+Scaffold; or (4) Allogeneic ASCs+Scaffold. Half of each group was sacrificed at 4 weeks postimplantation, and the remaining animals were sacrificed at 8 weeks. As determined in a separate study, allogeneic and syngeneic ASCs were equally efficacious in accelerating spinal fusion compared to No treatment and Scaffold only control groups. To determine whether donor ASCs induced an immune response in recipient rats, lymph nodes were harvested for T cell proliferation studies and serum was collected to assess antibody responses. Although T cell priming was not detected to donor alloantigens in recipients at either time point, significant antibody responses were detected to ACI ASCs in animals implanted with syngeneic or allogeneic ASCs. Antibodies were of the IgG isotype, noncytotoxic in the presence of complement, and reactive to fetal bovine serum. These results support the use of allogeneic ASCs for spinal fusion.