Over the past decade, the old idea that the bone marrow contains endothelial cell precursors has become an area of renewed interest. While some still believe that there are no endothelial precursors in the blood, even among those who do, there is no consensus as to what they are or what they do. In this review, we describe the problems in identifying endothelial cells and conclude that expression of endothelial nitric oxide synthase may be the most reliable antigenic indicator of the phenotype. The evidence for two different classes of endothelial precursors is also presented. We suggest that, though there is no single endothelial cell precursor, we may be able to use these phenotypic variations to our advantage in better understanding their biology. We also discuss how a variety of genetic, epigenetic, and methodological differences can account for the seemingly contradictory findings on the physiological relevance of bone marrow-derived precursors in normal vascular maintenance and in response to injury. Data on the impact of tumor type and location on the contribution of bone marrow-derived cells to the tumor vasculature are also presented. These data provide hope that we may ultimately be able to predict those tumors in which bone marrow-derived cells will have a significant contribution and design therapies accordingly. Finally, factors that regulate bone marrow cell recruitment to and function in the endothelium are beginning to be identified, and several of these, including stromal derived factor 1, monocyte chemoattractant factor-1, and vascular endothelial growth factor are discussed.

译文

在过去的十年中,骨髓含有内皮细胞前体的旧观念已成为人们重新关注的领域。尽管有些人仍然认为血液中没有内皮前体,即使在那些内皮前体中也是如此,但对于它们是什么或它们做什么还没有共识。在这篇综述中,我们描述了鉴定内皮细胞的问题,并得出结论,内皮一氧化氮合酶的表达可能是表型最可靠的抗原指标。还提供了两种不同类型的内皮前体的证据。我们建议,尽管没有单个内皮细胞前体,但我们可能能够利用这些表型变异来更好地了解它们的生物学。我们还讨论了各种遗传,表观遗传和方法上的差异如何解释关于骨髓来源的前体在正常血管维持和对损伤的反应中的生理相关性的看似矛盾的发现。还提供了有关肿瘤类型和位置对骨髓来源细胞对肿瘤脉管系统贡献的影响的数据。这些数据提供了希望,我们最终可能能够预测那些骨髓来源的细胞将在其中做出重大贡献的肿瘤,并相应地设计治疗方法。最后,开始确定调节骨髓细胞对内皮的募集和功能的因素,并讨论了其中的几种因素,包括基质衍生因子1,单核细胞趋化因子1和血管内皮生长因子。

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