Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California 94063, USA.
Tissue Eng Part A. 2012 May;18(9-10):968-73. doi: 10.1089/ten.TEA.2011.0545. Epub 2012 Jan 4.
Although iliac crest autologous bone graft remains the gold standard for treatment of bone defects, delayed- and nonunions, and arthrodeses, several alternative strategies have been attempted, including the use of mesenchymal stem cells. Whether cells from the osteoblast lineage demonstrate systemic recruitment to an acute bone defect or fracture, and whether these cells directly participate in bone healing is controversial. This study tests two hypotheses: (1) that exogenous murine MC3T3-E1 osteoprogenitor cells with a high propensity for osteoblast differentiation are able to systemically migrate to a bone defect and (2) that the migrated MC3T3-E1 cells enhance bone healing. Two groups of nude mice were used; a bone defect was drilled in the left femoral shaft in both groups. MC3T3-E1 were used as reporter cells and injected in the left ventricle of the heart, to avoid sequestration in the lungs. Injection of saline served as a control. We used bioluminescence and microCT to assay cell recruitment and bone mineral density (BMD). Immunohistochemical staining was used to confirm the migration of reporter cells. MC3T3-E1 cells were found to systemically migrate to the bone defect. Further, BMD at the defect was significantly increased when cells were injected. Systemic cell therapy using osteoprogenitor cells may be a potential strategy to enhance bone healing.
虽然髂嵴自体骨移植仍然是治疗骨缺损、延迟愈合和骨融合的金标准，但已经尝试了几种替代策略，包括使用间充质干细胞。成骨细胞系的细胞是否能系统地募集到急性骨缺损或骨折部位，以及这些细胞是否直接参与骨愈合，这是有争议的。本研究检验了两个假设：（1）具有高成骨分化倾向的外源性鼠 MC3T3-E1 成骨前体细胞能够系统地迁移到骨缺损部位；（2）迁移的 MC3T3-E1 细胞能促进骨愈合。本研究使用了两组裸鼠；在两组的左股骨骨干上钻了一个骨缺损。MC3T3-E1 被用作报告细胞，并注射到左心室，以避免被肺部隔离。注射生理盐水作为对照。我们使用生物发光和 microCT 来检测细胞募集和骨密度（BMD）。免疫组织化学染色用于确认报告细胞的迁移。发现 MC3T3-E1 细胞能系统地迁移到骨缺损部位。进一步的，当注射细胞时，缺损处的 BMD 显著增加。使用成骨前体细胞的全身细胞治疗可能是增强骨愈合的一种潜在策略。
