Effects of fibroblast growth factor-4 (k-FGF) on long-term cultures of human bone marrow cells.
Effects of fibroblast growth factor-4 (k-FGF) on long-term cultures of human bone marrow cells.
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DOI：
10.1182/blood.v87.4.1282.bloodjournal8741282
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发表时间：
1996-02
期刊：
影响因子：
20.3
通讯作者：
FL Quito;J. Beh;O. Bashayan;C. Basilico;R. Basch
中科院分区：
文献类型：
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作者：
FL Quito;J. Beh;O. Bashayan;C. Basilico;R. Basch
成纤维细胞生长因子-4（FGF-4）是由k-FGF/hst癌基因编码的高度促有丝分裂的蛋白质，其刺激多种间充质和神经外胚层来源的细胞的生长。向人长期骨髓培养物中添加FGF-4以剂量依赖性方式增加了基质层的细胞密度和培养物中造血集落形成细胞的数量。基质层中的造血持续长达8个月。红细胞生成维持长达4周，但粒细胞是主要的非粘附细胞类型。与对照培养物相比，用FGF处理的培养物具有增加的单核细胞数量，并且在连续培养8个月后仍可以检测到一些CD 14+、CD 45+单核细胞。生长因子的加入增加了基质层的生长速率，并似乎延缓了其衰老。在FGF-4存在下进行的传代培养物的平板接种效率增加了10倍，并且生长为相对均匀的单层。这些继代培养物保持支持造血的能力达数月，而不含FGF-4的未处理的继代培养物生长不稳定，并且通常在4至6周内失去支持造血的能力。继代培养后生长的改善大大提高了使用基质细胞单层的多潜能造血干细胞的有限稀释测定的可靠性。FGF-4的主要作用似乎是对长期骨髓培养物的基质细胞，但不能排除对造血祖细胞的直接作用。
Fibroblast growth factor-4 (FGF-4), a highly mitogenic protein encoded by the k-fgf/hst oncogene, stimulates the growth of a variety of cells of mesenchymal and neuroectodermal origin. Addition of FGF-4 to human long-term bone marrow cultures increased both the cell density of the stromal layer and the number of hematopoietic colony forming cells in the cultures in a dose-dependent manner. Hematopoiesis in the stromal layer persisted for up to 8 months. Erythropoiesis was maintained for up to 4 weeks, but granulocytes were the predominant nonadherent cell type. Cultures treated with FGF had increased numbers of monocytes compared with control cultures and some CD14+, CD45+ monocytes could still be detected after 8 months of continuous culture. The addition of the growth factor increased the rate of growth of the stromal layer and appeared to delay its senescence. Subcultures made in the presence of FGF-4 had up to 10-fold increases in plating efficiency and grew as relatively uniform monolayers. These subcultures retained the capacity to support hematopoiesis for several months, while untreated subcultures, made without FGF-4, grew erratically and generally lost the capacity to support hematopoiesis within 4 to 6 weeks. The improved growth after subculture greatly enhanced the reliability of limit-dilution assays of multipotential hematopoietic stem cells that use stromal cell monolayers. The primary effect of FGF-4 appeared to be on the stromal cells of the long-term bone marrow cultures, but a direct effect on hematopoietic progenitors could not be ruled out.