Heat Shock Protein-90 beta Is Expressed at the Surface of Multipotential Mesenchymal Precursor Cells: Generation of a Novel Monoclonal Antibody, STRO-4, With Specificity for Mesenchymal Precursor Cells From Human and Ovine Tissues
Heat Shock Protein-90 beta Is Expressed at the Surface of Multipotential Mesenchymal Precursor Cells: Generation of a Novel Monoclonal Antibody, STRO-4, With Specificity for Mesenchymal Precursor Cells From Human and Ovine Tissues
复制标题
DOI：
10.1089/scd.2008.0400
复制
发表时间：
2009-11-01
影响因子：
4
通讯作者：
Zannettino, Andrew C. W.
中科院分区：
文献类型：
--
作者：
Gronthos, Stan;McCarty, Rosa;Zannettino, Andrew C. W.
骨髓间充质干细胞（Mesenchymal stromal cells，MSCs）及其前体细胞（precursor cells，MPC）可增殖分化为多种中胚层和部分外胚层、内胚层组织。目前正在评估培养扩增的MSC作为一种可能的细胞疗法，以取代/修复受伤或患病的组织。虽然许多对人MSC具有特异性的mAb试剂，包括STR 0 -1、STR 0 -3（BLK ALP）、CD 71（SH 2、SH 3）、CD 106（VCAM-1）、CD 166和CD 271，已经促进了从原代组织中分离纯化的人MSC群体，但是很少有（如果有的话）mAb试剂被描述可以用于从其他物种中分离等同细胞。这在评估MSC在大型免疫活性、临床前疾病动物模型中的组织再生功效时特别相关。鉴于此，我们试图产生新的单克隆抗体（mAb），其对由来自不同物种的MSC以高水平表达的细胞表面分子具有特异性反应性。使用CD 106（VCAM-1）选择的绵羊MSC作为免疫原，选择产生mAb的杂交瘤，以确定其对人和绵羊MSC的反应性。一种这样的杂交瘤，称为STRO-4，产生与以下反应的IgG mAb：
Mesenchymal stromal cells (MSCs) and their precursor cells (MPCs) can proliferate and differentiate into multiple mesodermal and some ectodermal and endodermal tissues. Culture-expanded MSCs are currently being evaluated as a possible cell therapy to replace/repair injured or diseased tissues. While a number of mAb reagents with specificity to human MSCs, including STRO-1, STRO-3 (BLK ALP), CD71 (SH2, SH3), CD106 (VCAM-1), CD166, and CD271, have facilitated the isolation of purified populations of human MSCs from primary tissues, few if any mAb reagents have been described that can be used to isolate equivalent cells from other species. This is of particular relevance when assessing the tissue regenerative efficacy of MSCs in large immunocompetent, preclinical animal models of disease. In light of this, we sought to generate novel monoclonal antibodies (mAb) with specific reactivity against a cell surface molecule that is expressed at high levels by MSCs from different species. Using CD106 (VCAM-1)-selected ovine MSCs as an immunogen, mAb-producing hybridomas were selected for their reactivity to both human and ovine MSCs. One such hybridoma, termed STRO-4, produced an IgG mAb that reacted with