Stem Cells Genetically Modified With the Developmental Gene MT1-MMP Improve Regeneration of the Supraspinatus Tendon-to-Bone Insertion Site
Stem Cells Genetically Modified With the Developmental Gene MT1-MMP Improve Regeneration of the Supraspinatus Tendon-to-Bone Insertion Site
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DOI：
10.1177/0363546510361235
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发表时间：
2010-07-01
影响因子：
4.8
通讯作者：
Rodeo, Scott A.
中科院分区：
文献类型：
--
作者：
Gulotta, Lawrence V.;Kovacevic, David;Rodeo, Scott A.
背景：肩袖在修复后通过疤痕组织界面愈合，这使得它们容易失败。研究设计：对照实验室研究。方法：对60只Lewis大鼠进行单侧冈上肌腱分离和修复。30只动物接受纤维蛋白胶载体中的间充质干细胞(MSCs)，30只接受腺病毒MT1-MMP腺病毒(Ad-MT1-MMPs)转导的MSCs。动物在2周和4周时被处死，并评估在植入处是否存在纤维软骨和胶原纤维组织。进行生物力学测试，以确定修复组织的结构和材料特性。统计学处理采用Wilcoxon秩和检验，P=0.05。结果：在2周时，Ad-MT1-MMP组和MSC组之间的任何结果变量均无差异。4周时，Ad-MT1-MMP组较MSC组有更多的纤维软骨(P=.05)，更高的破坏极限载荷(P=.01)，更高的破坏极限应力(P=.005)和更高的刚度值(P=.02)。结论：转基因骨髓间充质干细胞过表达发育基因MT1-MMP4周时可通过在止点处出现更多的纤维软骨和提高生物力学强度来促进肩袖愈合。临床意义：MT1-基质金属蛋白酶转导的骨髓间充质干细胞对修复的肩袖进行生物强化可以减少再撕裂的发生率。然而，还需要进一步的研究来确定这种方法在更大的模型中是否仍然安全有效。
Background: Rotator cuffs heal through a scar tissue interface after repair, which makes them prone to failure. Membrane type 1 matrix metalloproteinase (MT1-MMP) is upregulated during embryogenesis in areas that develop into tendon-bone insertion sites.Hypothesis: Bone marrow-derived stem cells in the presence of the developmental signal from MT1-MMP will drive the healing process toward regeneration and away from scar formation.Study Design: Controlled laboratory study.Methods: Sixty Lewis rats underwent unilateral detachment and repair of the supraspinatus tendon. Thirty animals received mesenchymal stem cells (MSCs) in a fibrin glue carrier, and 30 received adenoviral MT1-MMP (Ad-MT1-MMP)-transduced MSCs. Animals were sacrificed at 2 weeks and 4 weeks and evaluated for the presence of fibrocartilage and collagen fiber organization at the insertion. Biomechanical testing was performed to determine the structural and material properties of the repaired tissue. Statistical analysis was performed with a Wilcoxon rank-sum test with significance set at P=.05.Results: There were no differences between the Ad-MT1-MMP and MSC groups in any outcome variable at 2 weeks. At 4 weeks, the Ad-MT1-MMP group had more fibrocartilage (P=.05), higher ultimate load to failure (P =.01), higher ultimate stress to failure (P=.005), and higher stiffness values (P=.02) as compared with the MSC group.Conclusion: Mesenchymal stem cells genetically modified to overexpress the developmental gene MT1-MMP can augment rotator cuff healing at 4 weeks by the presence of more fibrocartilage at the insertion and improved biomechanical strength. Clinical Relevance: Biologic augmentation of repaired rotator cuffs with MT1-MMP-transduced MSCs may reduce the incidence of retears. However, further studies are needed to determine if this remains safe and effective in larger models.