Cell-to-cell contact is critical for the survival of hematopoietic progenitor cells on osteoblasts
Cell-to-cell contact is critical for the survival of hematopoietic progenitor cells on osteoblasts
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DOI：
10.1016/j.cyto.2005.09.001
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发表时间：
2005-11-03
期刊：
影响因子：
3.8
通讯作者：
Taichman, RS
中科院分区：
文献类型：
--
作者：
Jung, Y;Wang, JH;Taichman, RS
成骨细胞构成骨髓中造血基质细胞支持系统的一部分，但人们对它们如何与造血干细胞（HSC）相互作用知之甚少。体外研究已经证明，HSC与成骨细胞共培养的存活需要密切的细胞间接触。这表明支持干细胞活性的成骨细胞衍生因子以非常小的量产生，快速翻转，可能是膜锚定的和/或需要细胞-细胞粘附分子的参与，这还有待确定。在本报告中，我们发现造血祖细胞在成骨细胞上的存活依赖于使用功能阻断抗体的VLA-4（α（4）β（1））和VLA-5（α（5）β（1））受体的接合。细胞与细胞的接触是支持祖细胞活性所必需的，但如果通过使用重组配体（纤连蛋白）提供VLA-4和LFA-1复合物的受体-配体接合，则可以被替代。ICAM-LVCAM-1）。此外，一旦这些受体参与，条件培养基来源于造血干细胞上生长的成骨细胞配体支持显着更大的造血祖细胞在体外比成骨细胞条件培养基或造血干细胞条件培养基单独。虽然存在于共培养培养基中的分子仍有待鉴定，但数据表明造血细胞与成骨细胞合作，通过指导成骨细胞衍生的细胞因子的合成来组装各种骨髓微环境，以改善HSC存活。(c)2005年爱思唯尔有限公司保留所有战斗。
Osteoblasts constitute part of the stromal cell support system in marrow for hematopoiesis, however little is known as to how they interact with hematopoietic stem cells (HSCs). In vitro studies have demonstrated that the survival of HSCs in co-culture with osteoblasts requires intimate cell-to-cell contact. This suggests that the osteoblast-derived factor(s) that supports stem cell activities are produced in very small quantities, are rapidly turned over, may be membrane-anchored and/or require the engagement of cell-cell adhesion molecules that are yet to be determined. In the present report we found that the survival of hematopoietic progenitor cells on osteoblasts is dependent upon the engagement of VLA-4 (alpha(4)beta(1)) and VLA-5 (alpha(5)beta(1)) receptors using function blocking antibodies. Cell-to-cell contact is required to support progenitor activity, but can be replaced if receptor-ligand engagement of the VLA-4 and LFA-1 complexes is provided through the use of recombinant ligands (fibronectin. ICAM-L VCAM-1). Moreover, once these receptors were engaged, conditioned medium derived from HSCs grown on osteoblast ligands supported significantly greater hematopoietic progenitors in vitro than did osteoblast-conditioned or HSC-conditioned medium alone. While the molecules present in the co-cultured medium remain to be identified, the data suggest that hematopoietic cells cooperate with osteoblasts to assemble the various marrow microenvironments by directing the synthesis of osteoblast-derived cytokines to improve HSC survival. (c) 2005 Elsevier Ltd. All fights reserved.