Williams D A, Rosenblatt M F, Beier D R, Cone R D
Division of Hematology-Oncology, Children's Hospital, Boston, Massachusetts.
Mol Cell Biol. 1988 Sep;8(9):3864-71. doi: 10.1128/mcb.8.9.3864-3871.1988.
The bone marrow is a complex microenvironment made up of multiple cell types which appears to play an important role in the maintenance of hematopoietic stem cell self-renewal and proliferation. We used murine long-term marrow cultures and a defective recombinant retrovirus vector containing the simian virus 40 large T antigen to immortalize marrow stromal cells which can support hematopoiesis in vitro for up to 5 weeks. Such cloned cell lines differentially supported stem cells which, when transplanted, allowed survival of lethally irradiated mice, formed hematopoietic spleen colonies in vivo, and stimulated lymphocyte proliferation in vitro. Molecular and functional analyses of these cell lines did not demonstrate the production of any growth factors known to support the proliferation of primitive hematopoietic stem cells. All cell lines examined produced macrophage colony-stimulating factor. The use of immortalizing retrovirus vectors may allow determination of unique cellular proteins important in hematopoietic stem cell proliferation by the systematic comparison of stromal cells derived from a variety of murine tissues.
骨髓是一个由多种细胞类型组成的复杂微环境，它似乎在维持造血干细胞的自我更新和增殖中发挥着重要作用。我们使用小鼠长期骨髓培养物和一种含有猿猴病毒40大T抗原的缺陷重组逆转录病毒载体，使能够在体外支持造血长达5周的骨髓基质细胞永生化。这种克隆细胞系对干细胞有不同的支持作用，这些干细胞在移植后能使受致死剂量照射的小鼠存活，在体内形成造血脾集落，并在体外刺激淋巴细胞增殖。对这些细胞系的分子和功能分析未显示产生任何已知支持原始造血干细胞增殖的生长因子。所有检测的细胞系都产生巨噬细胞集落刺激因子。通过对源自多种小鼠组织的基质细胞进行系统比较，使用永生化逆转录病毒载体可能有助于确定在造血干细胞增殖中重要的独特细胞蛋白。
