Lund Stem Cell Center, Lund University, 22184 Lund, Sweden.
Department of Endocrinology, University of Southern Denmark, Molecular Endocrinology Laboratory (KMEB), Odense 5000, Denmark.
Stem Cell Reports. 2014 Dec 9;3(6):965-74. doi: 10.1016/j.stemcr.2014.09.018. Epub 2014 Oct 30.
Human bone marrow (BM) contains a rare population of nonhematopoietic mesenchymal stromal cells (MSCs), which are of central importance for the hematopoietic microenvironment. However, the precise phenotypic definition of these cells in adult BM has not yet been reported. In this study, we show that low/negative expression of CD140a (PDGFR-α) on lin(-)/CD45(-)/CD271(+) BM cells identified a cell population with very high MSC activity, measured as fibroblastic colony-forming unit frequency and typical in vitro and in vivo stroma formation and differentiation capacities. Furthermore, these cells exhibited high levels of genes associated with mesenchymal lineages and HSC supportive function. Moreover, lin(-)/CD45(-)/CD271(+)/CD140a(low/-) cells effectively mediated the ex vivo expansion of transplantable CD34(+) hematopoietic stem cells. Taken together, these data indicate that CD140a is a key negative selection marker for adult human BM-MSCs, which enables to prospectively isolate a close to pure population of candidate human adult stroma stem/progenitor cells with potent hematopoiesis-supporting capacity.
人类骨髓（BM）中含有一种罕见的非造血间充质基质细胞（MSCs）群体，对于造血微环境至关重要。然而，这些细胞在成人 BM 中的精确表型定义尚未得到报道。在这项研究中，我们表明，lin(-)/CD45(-)/CD271(+) BM 细胞上低/阴性表达 CD140a（PDGFR-α）可鉴定出具有非常高 MSC 活性的细胞群体，其活性可通过成纤维细胞集落形成单位频率以及典型的体外和体内基质形成和分化能力来衡量。此外，这些细胞表现出与间充质谱系和 HSC 支持功能相关的高水平基因。此外，lin(-)/CD45(-)/CD271(+)/CD140a(low/-)细胞有效地介导了可移植 CD34(+)造血干细胞的体外扩增。综上所述，这些数据表明 CD140a 是成人人类 BM-MSCs 的关键负选择标记，可用于前瞻性分离具有强大造血支持能力的候选人类成人基质干细胞/祖细胞的近乎纯群体。
