Biology of bone marrow stroma
Biology of bone marrow stroma
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DOI：
10.1111/j.1749-6632.1995.tb31044.x
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发表时间：
1995-01-01
期刊：
影响因子：
--
通讯作者：
Keating, A
中科院分区：
文献类型：
--
作者：
Clark, BR;Keating, A
骨髓微环境是一个复杂的三维结构，由多种细胞类型和丰富的细胞外基质组成。大部分数据来自对小鼠，特别是人类长期骨髓培养的粘附层的分析。这种体外骨髓微环境的基本特征是存在扁平成角细胞，其功能定义为骨髓基质细胞，具有以下表型：IV型胶原（+），层粘连蛋白（+），波形蛋白（+），CD10(+)，肌动蛋白（+），Stro-1 (+), CD45， Mac-1和HLA-DR阴性。基质前体是Stro-1（+）和CD34（+）。微环境对造血前体的调节是通过调节分子（如造血细胞因子）的细化，通过粘附分子（如α 4 β 1整合素）的细胞-细胞接触，以及与细胞外基质组分的相互作用（如糖胺聚糖透明质酸与细胞相关CD44的相互作用）来实现的。虽然对骨髓基质细胞发育本身的调控知之甚少，但一些研究表明骨髓基质细胞在特定条件下具有可移植性。这些进展提示基质细胞在细胞治疗中的潜在作用。转染的基质细胞可以作为基因传递的合适载体，以纠正单基因疾病，其中靶基因的产物不需要严格调节，例如，在纠正因子VIII和因子IX缺乏症中。进一步研究骨髓基质细胞的生理和调控是必要的，以便更好地了解造血功能，并探索基质在治疗中的可能应用。
The marrow microenvironment is a complex, three-dimensional structure composed of many cell types and abundant extracellular matrix. Much of the data are derived from analysis of the adherent layer of murine and, especially, human long-term marrow cultures. An essential feature of this in vitro counterpart to the marrow microenvironment is the presence of flat angulated cells functionally defined as marrow stromal cells with the following phenotype: type IV collagen (+), laminin (+), vimentin (+), CD10 (+), muscle actin (+), Stro-1 (+), and negative for CD45, Mac-1, and HLA-DR. Stromal precursors are Stro-1 (+) and CD34 (+). Regulation of hematopoietic precursors by the microenvironment occurs by elaboration of regulatory molecules such as hematopoietic cytokines, by cell-cell contact via adhesion molecules such as alpha 4 beta 1 integrin, and by interactions with components of the extracellular matrix as in the case of the glycosaminoglycan hyaluronic acid with cell-associated CD44. Although little about the regulation of stromal cell development itself is known, several studies indicate the transplantability of marrow stromal cells under specific conditions. These developments suggest a potential role of stromal cells in cell therapy. Transfected stromal cells may serve as suitable vehicles for gene delivery to correct single gene disorders in which the product of the target gene does not require stringent regulation as, for example, in the correction of Factor VIII and Factor IX deficiency. Further studies are warranted to investigate marrow stromal cell physiology and regulation to better understand hematopoiesis and to explore the possible use of stroma in therapy.