Voermans C, van Hennik P B, van der Schoot C E
CLB, Sanquin Blood Supply Foundation and Laboratory for Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
J Hematother Stem Cell Res. 2001 Dec;10(6):725-38. doi: 10.1089/152581601317210827.
In healthy adults, hematopoiesis takes place in the bone marrow, where the majority of hematopoietic progenitor cells (HPC) reside. In patients undergoing chemo- and/or radiotherapy, hematopoiesis is seriously disturbed. Reconstitution of bone-marrow function can be achieved by bone marrow transplantation or peripheral blood stem cell transplantation. The success of stem cell transplantation depends on the ability of intravenously infused stem cells to lodge in the bone marrow, a process referred to as homing. However, the molecular mechanisms that govern this process are poorly understood. It is hypothesized that homing is a multistep process, consisting of adhesion of the HPC to endothelial cells of the marrow sinusoids, followed by transendothelial migration directed by chemoattractants, and finally anchoring within the extravascular bone marrow spaces where proliferation and differentiation will occur. In this review, we discuss the factors that determine the engraftment potential of stem cells, and focus on various aspects of migration and homing of HPC, i.e., the role of the chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR-4, the involvement of adhesion molecules, and the induction of actin polymerization in the HPC. Defining the role of chemokines and adhesion molecules in human stem cell migration and engraftment will help us uncover the underlying mechanisms that regulate stem cell homing and will eventually advance clinical stem cell transplantation.
在健康成年人中，造血过程发生在骨髓，大多数造血祖细胞（HPC）都存在于骨髓中。在接受化疗和/或放疗的患者中，造血功能受到严重干扰。骨髓功能的重建可以通过骨髓移植或外周血干细胞移植来实现。干细胞移植的成功取决于静脉输注的干细胞在骨髓中定居的能力，这一过程称为归巢。然而，控制这一过程的分子机制却知之甚少。据推测，归巢是一个多步骤过程，包括HPC与骨髓血窦内皮细胞的黏附，随后在趋化因子的引导下进行跨内皮迁移，最后锚定在血管外骨髓空间内，在那里将发生增殖和分化。在这篇综述中，我们讨论了决定干细胞植入潜力的因素，并重点关注HPC迁移和归巢的各个方面，即趋化因子基质细胞衍生因子-1（SDF-1）及其受体CXCR-4的作用、黏附分子的参与以及HPC中肌动蛋白聚合的诱导。明确趋化因子和黏附分子在人类干细胞迁移和植入中的作用，将有助于我们揭示调节干细胞归巢的潜在机制，并最终推动临床干细胞移植的发展。
