Tendon-to-Bone Healing in a Rat Extra-articular Bone Tunnel Model: A Comparison of Fresh Autologous Bone Marrow and Bone Marrow-Derived Mesenchymal Stem Cells
Tendon-to-Bone Healing in a Rat Extra-articular Bone Tunnel Model: A Comparison of Fresh Autologous Bone Marrow and Bone Marrow-Derived Mesenchymal Stem Cells
复制标题
大鼠关节外骨隧道模型中的腱骨愈合：新鲜自体骨髓和骨髓间充质干细胞的比较
DOI：
10.1177/0363546519862284
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发表时间：
2019-07-24
影响因子：
4.8
通讯作者：
Vanderby, Ray
中科院分区：
文献类型：
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作者：
Lu, Jun;Chamberlain, Connie S.;Vanderby, Ray
背景资料：尽管临床实践中广泛接受新鲜自体骨髓（BM），但分析局部使用新鲜自体骨髓是否可以加速肌腱-骨愈合的信息有限。目的：研究新鲜自体骨髓对大鼠肌腱-骨愈合的影响。研究设计：对照实验室研究。方法：在骨骼成熟的Sprague-Dawley大鼠（N = 60）中创建关节外骨隧道并填充自体肌腱移植物。随机分为3组：骨髓组（20例）（肌腱-骨界面注射新鲜自体骨髓）、骨髓间充质干细胞（BMSC）组（20例）（注射同种异体培养的BMSC）和对照组（肌腱-骨界面不注射骨髓或BMSC）。在术后2周和6周进行生物力学、组织学和免疫组织化学分析。结果如下：与BMSC组相比，BM组显示出相对组织良好和致密的结缔组织界面，具有更好的胶原纤维取向。2周时，BMSC组的腱-骨界面组织厚度为140 ± 25 μm（平均值± SEM），显著大于BM组（58 ± 15 μm）。BM组在第2周和第6周肌腱-骨界面处的M1巨噬细胞较少（P < .001）。相反，与对照组和BMSC组相比，术后2周和6周BM组界面处有更多的M2巨噬细胞（P < .001）。生物力学测试显示，与对照组和BMSC组相比，BM组在术后2周和6周时的刚度显著更高（P <0.05）。失效载荷与刚度的趋势相似。结论：这些发现表明，在本研究中，新鲜自体BM的局部递送比替代治疗更好地促进腱-骨愈合。这种作用可能部分是由于观察到的炎症过程的调节，特别是在M2巨噬细胞极化。临床相关性：新鲜自体骨髓可能是这种疾病的治疗选择。
Background: Despite widespread acceptance of fresh autologous bone marrow (BM) for use in clinical practice, limited information exists to analyze if tendon-to-bone healing could be accelerated with local use of fresh autologous BM. Purpose: To investigate the effect of fresh autologous BM on tendon-to-bone healing with a novel rat model. Study Design: Controlled laboratory study. Methods: An extra-articular bone tunnel was created and filled with an autologous tendon graft in skeletally mature Sprague-Dawley rats (N = 60). They were then randomly divided into 3 groups: BM group (injection of fresh autologous BM into the tendon-bone interface, n = 20), BM-derived mesenchymal stem cell (BMSC) group (injection of allogenic cultured BMSCs, n = 20), and the control group (tendon-bone interface without injection of BM or BMSCs, n = 20). Biomechanical, histological, and immunohistochemical analyses were performed at 2 and 6 weeks after surgery. Results: The BM group showed a relatively well-organized and dense connective tissue interface with better orientation of collagen fibers as compared with the BMSC group. At 2 weeks, the tendon-bone interface tissue thickness of the BMSC group was 140 ± 25 μm (mean ± SEM), which was significantly greater than the BM group (58 ± 15 μm). The BM group showed fewer M1 macrophages at the tendon-bone interface at 2 and 6 weeks (P < .001). In contrast, there were more M2 macrophages at the interface in the BM group 2 and 6 weeks postoperatively when compared with controls and the BMSC group (P < .001). Biomechanical tests revealed significantly higher stiffness in the BM group versus the control and BMSC groups at 2 and 6 weeks after surgery (P < .05). Load to failure showed similar trends to stiffness. Conclusion: These findings indicate that local delivery of fresh autologous BM enhances tendon-to-bone healing better than the alternative treatments in this study. This effect may be partially due to the observed modulation of inflammatory processes, especially in M2 macrophage polarization. Clinical Relevance: Fresh autologous BM could be a treatment option for this disorder.