Umbilical cord tissue provides a unique source of cells with potential for tissue repair. Umbilical cord tissue-derived cells (UTCs) are MHC class I (MHCI) dull and negative for MHC class II (MHCII), but can be activated to increase MHCI and to express MHCII with IFN-gamma stimulation. Mesenchymal stem cells with similar characteristics have been inferred to be nonimmunogenic; however, in most cases, immunogenicity was not directly assessed. Using UTC from Massachusetts General Hospital MHC-defined miniature swine, we assessed immunogenicity across a full MHC barrier. Immunogenicity was assessed by in vitro assays including mixed lymphocyte reaction (MLR) and flow cytometry to detect serum alloantibody. A single injection of MHC-mismatched unactivated UTCs did not induce a detectable immune response. When injected in an inflamed region, injected repeatedly in the same region or stimulated with IFN-gamma prior to injection, UTCs were immunogenic. As clinical cellular repair strategies may involve injection of allogeneic cells into inflamed regions of damaged tissue or repeated doses of cells to achieve the desired benefit, our results on the immunogenicity of these cells in these circumstances may have important implications for optimal success and functional improvement for this cellular treatment strategy for diseased tissues.

译文

:脐带组织提供了独特的细胞来源,具有组织修复的潜力。脐带组织来源的细胞(UTC)是MHC I类(MHCI)呆滞,而MHC II类(MHCII)阴性,但是可以被激活以增加MHCI并通过IFN-γ刺激表达MHCII。具有相似特征的间充质干细胞已被推断为非免疫原性的。但是,在大多数情况下,没有直接评估免疫原性。使用马萨诸塞州总医院MHC定义的微型猪的UTC,我们评估了整个MHC屏障的免疫原性。通过体外测定,包括混合淋巴细胞反应(MLR)和流式细胞仪检测血清同种抗体,评估免疫原性。一次注射MHC不匹配的未激活UTC不会诱导可检测到的免疫反应。当在发炎区域注射,在同一区域重复注射或在注射前用IFN-γ刺激时,UTC具有免疫原性。由于临床细胞修复策略可能涉及将同种异体细胞注射到受损组织的发炎区域或重复剂量的细胞中以获得所需的益处,因此我们在这些情况下对这些细胞的免疫原性的研究结果可能对获得最佳成功和功能改善具有重要意义。这种针对患病组织的细胞治疗策略。

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