Choo Andre B, Tan Heng Liang, Ang Sheu Ngo, Fong Wey Jia, Chin Angela, Lo Jennifer, Zheng Lu, Hentze Hannes, Philp Robin J, Oh Steve K W, Yap Miranda
Stem Cell Group, Bioprocessing Technology Institute, 20 Biopolis Way #06-01, Singapore.
Stem Cells. 2008 Jun;26(6):1454-63. doi: 10.1634/stemcells.2007-0576. Epub 2008 Mar 20.
Future therapeutic applications of differentiated human embryonic stem cells (hESC) carry a risk of teratoma formation by contaminating undifferentiated hESC. We generated 10 monoclonal antibodies (mAbs) against surface antigens of undifferentiated hESC, showing strong reactivity against undifferentiated, but not differentiated hESC. The mAbs did not cross react with mouse fibroblasts and showed weak to no reactivity against human embryonal carcinoma cells. Notably, one antibody (mAb 84) is cytotoxic to undifferentiated hESC and NCCIT cells in a concentration-dependent, complement-independent manner. mAb 84 induced cell death of undifferentiated, but not differentiated hESC within 30 minutes of incubation, and immunoprecipitation of the mAb-antigen complex revealed that the antigen is podocalyxin-like protein-1. Importantly, we observed absence of tumor formation when hESC and NCCIT cells were treated with mAb 84 prior to transplantation into severe combined immunodeficiency mice. Our data indicate that mAb 84 may be useful in eliminating residual hESC from differentiated cells populations for clinical applications. Disclosure of potential conflicts of interest is found at the end of this article.
分化的人胚胎干细胞（hESC）未来的治疗应用存在因未分化的hESC污染而形成畸胎瘤的风险。我们制备了10种针对未分化hESC表面抗原的单克隆抗体（mAb），这些抗体对未分化的hESC有强烈反应，但对分化的hESC无反应。这些单克隆抗体与小鼠成纤维细胞无交叉反应，对人胚胎癌细胞的反应较弱或无反应。值得注意的是，一种抗体（mAb 84）以浓度依赖性、非补体依赖性方式对未分化的hESC和NCCIT细胞具有细胞毒性。mAb 84在孵育30分钟内可诱导未分化而非分化的hESC发生细胞死亡，对mAb - 抗原复合物进行免疫沉淀显示该抗原是足突蛋白样蛋白-1。重要的是，我们观察到在将hESC和NCCIT细胞移植到严重联合免疫缺陷小鼠之前用mAb 84处理后未形成肿瘤。我们的数据表明，mAb 84可能有助于从分化细胞群体中消除残留的hESC以用于临床应用。潜在利益冲突的披露见本文末尾。
