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首页> 外文期刊>Cytokine >Cell-to-cell contact is critical for the survival of hematopoietic progenitor cells on osteoblasts.
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Cell-to-cell contact is critical for the survival of hematopoietic progenitor cells on osteoblasts.

机译：细胞之间的接触对于造血祖细胞在成骨细胞上的存活至关重要。

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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 (alpha4beta1) and VLA-5 (alpha5beta1) 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-1, 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.
机译：成骨细胞是骨髓中造血作用的基质细胞支持系统的一部分，然而，关于成骨细胞与造血干细胞（HSC）相互作用的方式知之甚少。体外研究表明，HSC与成骨细胞共培养的存活需要紧密的细胞间接触。这表明支持干细胞活性的成骨细胞衍生因子的产生非常少，被迅速翻转，可能被膜锚定和/或需要细胞细胞粘附分子的参与。决心。在本报告中，我们发现成骨细胞上造血祖细胞的存活依赖于使用功能阻断抗体的VLA-4（alpha4beta1）和VLA-5（alpha5beta1）受体的参与。需要细胞间接触来支持祖细胞活性，但是如果通过使用重组配体（纤连蛋白，ICAM-1，VCAM-1）提供了VLA-4和LFA-1复合物的受体-配体结合，则可以替代细胞间的接触）。此外，一旦这些受体结合，与成骨细胞条件或HSC条件培养基相比，在成骨细胞配体上生长的HSC衍生的条件培养基在体外即可支持更大的造血祖细胞。虽然存在于共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协同作用，通过指导成骨细胞衍生的细胞因子的合成来改善HSC存活，从而组装了各种骨髓微环境。

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