Atlanta Veteran Affairs Medical Center and Department of Orthopaedics, Emory University School of Medicine, Atlanta, Georgia, USA.
Tissue Eng Part A. 2011 Feb;17(3-4):523-30. doi: 10.1089/ten.tea.2010.0168. Epub 2010 Nov 2.
The mechanisms driving bone marrow stem cell mobilization are poorly understood. A recent murine study found that circulating bone marrow-derived osteoprogenitor cells (MOPCs) were recruited to the site of recombinant human bone morphogenetic protein-2 (BMP-2)-induced bone formation. Stromal cell-derived factor-1α (SDF-1α) and its cellular receptor CXCR4 have been shown to mediate the homing of stem cells to injured tissues. We hypothesized that chemokines, such as SDF-1, are also involved with mobilization of bone marrow cells. The CD45(-) fraction is a major source of MOPCs. In this report we determined that the addition of BMP-2 or SDF-1 to collagen implants increased the number of MOPCs in the peripheral blood. BMP-2-induced mobilization was blocked by CXCR4 antibody, confirming the role of SDF-1 in mobilization. We determined for the first time that addition of SDF-1 to implants containing BMP-2 enhances mobilization, homing of MOPCs to the implant, and ectopic bone formation induced by suboptimal BMP-2 doses. These results suggest that SDF-1 increases the number of osteoprogenitor cells that are mobilized from the bone marrow and then home to the implant. Thus, addition of SDF-1 to BMP-2 may improve the efficiency of BMPs in vivo, making their routine use for orthopaedic applications more affordable and available to more patients.
骨髓干细胞动员的机制尚未完全阐明。最近的一项鼠类研究发现，循环骨髓来源的成骨前体细胞（MOPC）被招募到重组人骨形态发生蛋白-2（BMP-2）诱导的骨形成部位。基质细胞衍生因子-1α（SDF-1α）及其细胞受体 CXCR4 已被证明介导干细胞归巢到受损组织。我们假设趋化因子（如 SDF-1）也参与骨髓细胞的动员。CD45(-) 部分是 MOPC 的主要来源。在本报告中，我们确定 BMP-2 或 SDF-1 添加到胶原植入物中会增加外周血中 MOPC 的数量。CXCR4 抗体阻断了 BMP-2 诱导的动员，证实了 SDF-1 在动员中的作用。我们首次确定，在含有 BMP-2 的植入物中添加 SDF-1 可增强动员、MOPC 向植入物的归巢以及亚最佳 BMP-2 剂量诱导的异位骨形成。这些结果表明，SDF-1 增加了从骨髓动员的成骨前体细胞的数量，然后归巢到植入物。因此，向 BMP-2 中添加 SDF-1 可能会提高 BMP 在体内的效率，从而使它们在骨科应用中的常规使用更实惠，更多患者受益。
