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大鼠脊柱融合模型中同种异体脂肪来源干细胞的免疫原性

Immunogenicity of allogeneic adipose-derived stem cells in a rat spinal fusion model.

作者信息

McIntosh Kevin R, Lopez Mandi J, Borneman Jade N, Spencer Nakia D, Anderson Paul A, Gimble Jeffrey M

机构信息

Cognate BioServices, Inc, Baltimore, Maryland 21227, USA.

出版信息

Tissue Eng Part A. 2009 Sep;15(9):2677-86. doi: 10.1089/ten.TEA.2008.0566.

Abstract

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.

摘要

脂肪来源干细胞(ASCs)呈现出非免疫原性特征,体外研究表明,对异体ASCs缺乏T细胞增殖反应,并且ASCs可介导混合淋巴细胞反应的抑制。为了确定这些观察结果在体内是否成立,结合大鼠脊柱融合研究开展了免疫监测研究。将源自Fischer或ACI品系大鼠的ASCs加载到支架上,并植入接受了以下处理的Fischer受体大鼠体内:(1)不处理;(2)仅植入支架;(3)同基因ASCs+支架;或(4)异基因ASCs+支架。每组动物的一半在植入后4周处死,其余动物在8周处死。在另一项研究中确定,与不处理组和仅植入支架的对照组相比,异基因和同基因ASCs在加速脊柱融合方面同样有效。为了确定供体ASCs是否在受体大鼠中诱导免疫反应,采集淋巴结进行T细胞增殖研究,并收集血清以评估抗体反应。尽管在两个时间点的受体中均未检测到对供体同种异体抗原的T细胞致敏,但在植入同基因或异基因ASCs的动物中检测到对ACI ASCs的显著抗体反应。抗体为IgG同种型,在补体存在下无细胞毒性,并且与胎牛血清反应。这些结果支持使用异基因ASCs进行脊柱融合。

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