Gronthos Stan, Fitter Stephen, Diamond Peter, Simmons Paul J, Itescu Silviu, Zannettino Andrew C W
Mesenchymal Research Laboratory, Division of Haematology, Institute of Medical and Veterinary Science, Hanson Institute and University of Adelaide, Australia 5000.
Stem Cells Dev. 2007 Dec;16(6):953-63. doi: 10.1089/scd.2007.0069.
Numerous studies support the concept that the nonhemopoietic cells of the bone marrow (BM), are derived from a population of multipotent bone marrow stromal stem cells (BMSSCs), which reside in perivascular niches within the bone marrow. These BMSSCs are thought to give rise not only to more cells that are phenotypically and functionally identical but also differentiated, lineage-committed mesenchymal progeny, including chondrocytes, smooth muscle cells, adipocytes, and osteoblasts. Recently, we have generated a novel monoclonal antibody (mAb) (designated STRO-3) that reacts with a minor subset of STRO-1(+) cells contained within adult BM aspirates and does not react with CD34(+) hemopoietic stem cells. Our results also show that STRO-3 identifies a high proportion of BMSSCs that possess extensive proliferative and multilineage differentiative capacity. Using retroviral expression cloning, we determined that STRO-3 binds to tissue nonspecific alkaline phosphatase (TNSALP), a cell-surface glycoprotein usually associated with cells of the osteoblast lineage. Studies presented here suggest that in addition to being expressed by osteoblasts, TNSALP may also represent a marker of immature BMSSCs in vivo. Finally, these studies suggest that antibodies to TNSALP may be used as an effective single marker of enrichment of BMSSCs from various tissues.
众多研究支持这样一种观点，即骨髓的非造血细胞源自一群多能骨髓基质干细胞（BMSSCs），它们存在于骨髓内的血管周围微环境中。这些BMSSCs不仅被认为能产生更多表型和功能相同的细胞，还能产生分化的、定向谱系的间充质后代，包括软骨细胞、平滑肌细胞、脂肪细胞和成骨细胞。最近，我们制备了一种新型单克隆抗体（mAb）（命名为STRO-3），它与成人骨髓抽吸物中包含的一小部分STRO-1(+)细胞发生反应，而不与CD34(+)造血干细胞发生反应。我们的结果还表明，STRO-3识别出了很大比例的具有广泛增殖和多谱系分化能力的BMSSCs。通过逆转录病毒表达克隆，我们确定STRO-3与组织非特异性碱性磷酸酶（TNSALP）结合，TNSALP是一种通常与成骨细胞谱系细胞相关的细胞表面糖蛋白。本文提出的研究表明，除了由成骨细胞表达外，TNSALP在体内可能还代表未成熟BMSSCs的一种标志物。最后，这些研究表明，针对TNSALP的抗体可作为从各种组织中富集BMSSCs的有效单一标志物。
