Approaches to avoid immune responses induced by repeated subcutaneous injections of allogeneic umbilical cord tissue-derived cells.
Approaches to avoid immune responses induced by repeated subcutaneous injections of allogeneic umbilical cord tissue-derived cells.
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DOI：
10.1097/tp.0b013e3181c6ff73
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发表时间：
2010-09-15
期刊：
影响因子：
6.2
通讯作者：
Huang CA
中科院分区：
文献类型：
--
作者：
Lutton BV;Cho PS;Hirsh EL;Ferguson KK;Teague AG;Hanekamp JS;Chi N;Goldman SN;Messina DJ;Houser S;Yeap BY;Popma SH;Sachs DH;Huang CA
用于修复病变组织的细胞治疗代表了一种有前途的临床策略。脐带组织来源的细胞（UTC）是一种独特的细胞来源，具有低免疫原性和组织修复潜力。通过使用来自小型猪的UTC，我们先前证明，尽管它们的免疫原性表型低，但UTC可以在某些炎症条件下和多次皮下（SC）注射后诱导免疫应答。鉴于重复给药细胞可能是实现持久治疗益处所必需的，在本研究中，我们检查了避免对多次SC注射UTC产生免疫应答的方法。通过使用体外和体内对SC细胞注射致敏的措施，我们评估了不同给药部位位置、延长注射间隔时间和使用免疫抑制剂治疗对马萨诸塞州总医院主要组织相容性复合体定义的小型猪重复细胞注射的影响。尽管在正常条件下，单次SC注射主要组织相容性复合物错配的UTC未诱导可检测的免疫应答，但多次SC注射UTC显示出快速的体液和细胞介导的免疫应答。通过每次UTC给药同时进行免疫抑制，避免了对重复SC注射的免疫应答。UTC和其他被认为是非免疫原性的类似细胞类型在某些条件下具有诱导免疫应答的潜力。这些研究为研究同种异体细胞疗法的临床前研究提供了重要的考虑因素和指南。
Cellular treatments for repairing diseased tissues represent a promising clinical strategy. Umbilical cord tissue-derived cells (UTC) are a unique source of cells with a low immunogenic profile and potential for tissue repair. By using UTC from miniature swine, we previously demonstrated that despite their low immunogenic phenotype, UTC could induce an immune response under certain inflammatory conditions and after multiple subcutaneous (SC) injections. Given that repeat dosing of cells may be necessary to achieve a lasting therapeutic benefit, in this study, we examined approaches to avoid an immune response to multiple SC injections of UTC. By using in vitro and in vivo measures of sensitization to SC cellular injections, we assessed the effects of varying the location of administration site, prolongation of timing between injections, and use of immunosuppressive treatments on repeated cellular injections in Massachusetts General Hospital major histocompatibility complex-defined miniature swine. Although under normal conditions, a single SC injection of major histocompatibility complex-mismatched UTC did not induce a detectable immune response, multiple SC injections of UTC demonstrated rapid humoral and cell-mediated immune responses. Avoidance of an immune response to repeat SC injection was achieved by concurrent immunosuppression with each dose of UTC. UTC and other similar cell types believed to be nonimmunogenic have the potential to induce immune responses under certain conditions. These studies provide important considerations and guidelines for preclinical studies investigating allogeneic cellular therapies.