Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, Illinois 60612, USA.
Tissue Eng Part A. 2012 Apr;18(7-8):860-9. doi: 10.1089/ten.TEA.2011.0187. Epub 2012 Jan 4.
Enhancement of in vivo mobilization and homing of endogenous mesenchymal stem cells (MSCs) to an injury site is an innovative strategy for improvement of bone tissue engineering and repair. The present study was designed to determine whether mobilization by AMD3100 and/or local homing by delivery of stromal cell-derived factor-1 (SDF-1) enhances recombinant human bone morphogenetic protein-2 (rhBMP-2) induced ectopic bone formation in an established rat model. Rats received an injection of either saline or AMD3100 treatment 1 h before harvesting of bone marrow for in vitro colony-forming unit-fibroblasts (CFU-F) culture or the in vivo subcutaneous implantation of absorbable collagen sponges (ACSs) loaded with saline, recombinant human bone morphogenetic protein-2 (rhBMP-2), SDF-1, or the combination of SDF-1 and rhBMP-2. AMD3100 treatment resulted in a significant decrease in CFU-F number, compared with saline, which confirmed that a single systemic AMD3100 treatment rapidly mobilized MSCs from the bone marrow. At 28 and 56 days, bone formation in the explanted ACS was assessed by microcomputed tomography (μCT) and histology. At 28 days, AMD3100 and/or SDF-1 had no statistically significant effect on bone volume (BV) or bone mineral content (BMC), but histology revealed more active bone formation with treatment of AMD3100, loading of SDF-1, or the combination of both AMD3100 and SDF-1, compared with saline-treated rhBMP-2 loaded ACS. At 56 days, the addition of AMD3100 treatment, loading of SDF-1, or the combination of both resulted in a statistically significant stimulatory effect on BV and BMC, compared with the saline-treated rhBMP-2 loaded ACS. Histology of the 56-day ACS were consistent with the μCT analysis, exhibiting more mature and mineralized bone formation with AMD3100 treatment, SDF-1 loading, or the combination of both, compared with the saline-treated rhBMP-2 loaded ACS. The present study is the first that provides evidence of the efficacy of AMD3100 and SDF-1 treatment to stimulate trafficking of MSCs to an ectopic implant site, in order to ultimately enhance rhBMP-2 induced long-term bone formation.
增强内源性间充质干细胞（MSCs）向损伤部位的体内迁移和归巢是改善骨组织工程和修复的创新策略。本研究旨在确定 AMD3100 动员和/或基质细胞衍生因子-1（SDF-1）的局部归巢是否增强了重组人骨形态发生蛋白-2（rhBMP-2）在已建立的大鼠模型中的异位骨形成。大鼠在收获骨髓进行体外集落形成单位-成纤维细胞（CFU-F）培养或可吸收胶原海绵（ACS）的体内皮下植入之前 1 小时接受盐水或 AMD3100 治疗，ACS 负载盐水、重组人骨形态发生蛋白-2（rhBMP-2）、SDF-1 或 SDF-1 和 rhBMP-2 的组合。AMD3100 处理导致 CFU-F 数量与盐水相比显著减少，这证实了单次全身 AMD3100 处理可迅速从骨髓中动员 MSCs。在 28 天和 56 天时，通过微计算机断层扫描（μCT）和组织学评估植入 ACS 中的骨形成。在 28 天时，AMD3100 和/或 SDF-1 对骨体积（BV）或骨矿物质含量（BMC）没有统计学上的显著影响，但组织学显示与盐水处理的 rhBMP-2 负载 ACS 相比，AMD3100 处理、SDF-1 加载或两者的组合具有更活跃的骨形成。在 56 天时，与盐水处理的 rhBMP-2 负载 ACS 相比，添加 AMD3100 处理、SDF-1 加载或两者的组合对 BV 和 BMC 具有统计学上的刺激作用。56 天 ACS 的组织学与 μCT 分析一致，与盐水处理的 rhBMP-2 负载 ACS 相比，AMD3100 处理、SDF-1 加载或两者的组合具有更成熟和矿化的骨形成。本研究首次提供了 AMD3100 和 SDF-1 治疗刺激 MSCs 向异位植入部位迁移的功效证据，以最终增强 rhBMP-2 诱导的长期骨形成。
