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关节外骨隧道模型中肌腱到骨的愈合:新鲜自体骨髓与骨髓间充质干细胞的比较。

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.

机构信息

Department of Orthopaedic Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.

Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, Wisconsin, USA.

出版信息

Am J Sports Med. 2019 Sep;47(11):2729-2736. doi: 10.1177/0363546519862284. Epub 2019 Jul 24.

DOI:10.1177/0363546519862284
PMID:31339739
Abstract

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 ( < .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 ( < .001). Biomechanical tests revealed significantly higher stiffness in the BM group versus the control and BMSC groups at 2 and 6 weeks after surgery ( < .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.

摘要

背景

尽管新鲜自体骨髓(BM)广泛应用于临床实践,但关于其是否能加速肌腱-骨愈合的信息有限。

目的

通过一种新型大鼠模型来研究新鲜自体 BM 对肌腱-骨愈合的影响。

研究设计

对照实验研究。

方法

在成熟的 Sprague-Dawley 大鼠(N = 60)中建立关节外骨隧道,并填充自体肌腱移植物。然后将它们随机分为 3 组:BM 组(向肌腱-骨界面注射新鲜自体 BM,n = 20)、BM 衍生间充质干细胞(BMSC)组(注射同种异体培养的 BMSCs,n = 20)和对照组(肌腱-骨界面不注射 BM 或 BMSCs,n = 20)。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

与 BMSC 组相比,BM 组的连接组织界面更有序、更密集,胶原纤维的方向更好。术后 2 周时,BMSC 组的肌腱-骨界面组织厚度为 140 ± 25 μm(均值 ± 标准差),明显大于 BM 组(58 ± 15 μm)。在术后 2 周和 6 周时,BM 组肌腱-骨界面的 M1 巨噬细胞较少(<.001)。相反,与对照组和 BMSC 组相比,BM 组在术后 2 周和 6 周时界面的 M2 巨噬细胞更多(<.001)。生物力学测试显示,术后 2 周和 6 周时,BM 组的刚度明显高于对照组和 BMSC 组(<.05)。失效负荷也表现出与刚度相似的趋势。

结论

这些发现表明,与本研究中的其他治疗方法相比,局部应用新鲜自体 BM 能更好地促进肌腱-骨愈合。这种效果可能部分归因于观察到的炎症过程的调节,尤其是 M2 巨噬细胞的极化。

临床相关性

新鲜自体 BM 可能是治疗这种疾病的一种选择。

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