Ho Chih-Yuan, Sanghani Anita, Hua Jia, Coathup Melanie, Kalia Priya, Blunn Gordon
Division of Surgery and Interventional Sciences, Institute of Orthopaedics and Musculoskeletal Science, The John Scales Centre for Biomedical Engineering, University College London , Royal National Orthopaedic Hospital, Stanmore, United Kingdom .
Tissue Eng Part A. 2015 Feb;21(3-4):594-602. doi: 10.1089/ten.TEA.2013.0762. Epub 2014 Nov 13.
Treatment of critical size bone defects pose a challenge in orthopedics. Stem cell therapy together with cytokines has the potential to improve bone repair as they cause the migration and homing of stem cells to the defect site. However, the engraftment, participation, and recruitment of other cells within the regenerating tissue are important. To enhance stem cell involvement, this study investigated overexpression of stem cells with stromal cell-derived factor 1 (SDF-1) using an adenovirus. We hypothesized that these engineered cells would effectively increase the migration of native cells to the site of fracture, enhancing bone repair. Before implantation, we showed that SDF-1 secreted by transfected cells increased the migration of nontransfected cells. In a rat defect bone model, bone marrow mesenchymal stem cells overexpressing SDF-1 showed significantly (p=0.003) more new bone formation within the gap and less bone mineral loss at the area adjacent to the defect site during the early bone healing stage. In conclusion, SDF-1 was shown to play an important role in accelerating fracture repair and contributing to bone repair in rat models, by recruiting more host stem cells to the defect site and encouraging osteogenic differentiation and production of bone.
治疗临界尺寸骨缺损是骨科领域的一项挑战。干细胞疗法与细胞因子相结合有改善骨修复的潜力，因为它们能促使干细胞迁移并归巢至缺损部位。然而，再生组织中其他细胞的植入、参与和募集也很重要。为增强干细胞的参与度，本研究使用腺病毒研究了通过基质细胞衍生因子1（SDF-1）使干细胞过表达的情况。我们假设这些工程细胞能有效增加天然细胞向骨折部位的迁移，从而促进骨修复。在植入前，我们发现转染细胞分泌的SDF-1能增加未转染细胞的迁移。在大鼠骨缺损模型中，过表达SDF-1的骨髓间充质干细胞在早期骨愈合阶段，间隙内新骨形成显著增多（p = 0.003），缺损部位相邻区域的骨矿物质流失减少。总之，在大鼠模型中，SDF-1通过招募更多宿主干细胞至缺损部位并促进成骨分化和骨生成，在加速骨折修复和促进骨修复方面发挥了重要作用。
