Effect of adipose-derived stromal cells and BMP12 on intrasynovial tendon repair: A biomechanical, biochemical, and proteomics study.
Effect of adipose-derived stromal cells and BMP12 on intrasynovial tendon repair: A biomechanical, biochemical, and proteomics study.
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DOI：
10.1002/jor.23064
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发表时间：
2016-04
期刊：
影响因子：
--
通讯作者：
Thomopoulos S
中科院分区：
文献类型：
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作者：
Gelberman RH;Shen H;Kormpakis I;Rothrauff B;Yang G;Tuan RS;Xia Y;Sakiyama-Elbert S;Silva MJ;Thomopoulos S
屈肌腱修复的结果是高度可变的。由于最近的努力，以改善愈合已经证明了基于生长因子和细胞的治疗的前景，目前的研究的目的是通过应用自体脂肪来源的基质细胞（ASC）和肌腱生长因子骨形态发生蛋白（BMP）12来增强修复。在临床相关的犬模型中使用基于纤维蛋白/纤维蛋白的支架实现细胞和生长因子的受控递送。对照组包括仅修复（无支架）和脱细胞支架。愈合28天后，使用生物力学，生物化学和蛋白质组学分析评估修复。与正常组相比，接受支架的组的运动范围减少。与仅修复相比，ASC+ BMP 12治疗对活动度或拉伸性能结果没有影响。生化分析表明，与正常组相比，所有修复组中的DNA、糖胺聚糖和交联浓度增加，但ASC+ BMP 12没有影响。与正常相比，脱细胞支架组中的总胶原蛋白显著降低，而与脱细胞支架组相比，ASC+ BMP 12组中的总胶原蛋白显著增加。比较愈合肌腱和未受伤肌腱的蛋白质组学分析显示，与炎症、应激反应和基质降解相关的蛋白质显著增加。ASC+ BMP 12处理放大了这些不利的变化。总之，本研究中使用的治疗方法在修复部位诱导了阴性炎症反应，导致愈合不良。未来的方法应该考虑细胞和生长因子的输送方法，不会引起负面的局部反应。
The outcomes of flexor tendon repair are highly variable. As recent efforts to improve healing have demonstrated promise for growth factor- and cell-based therapies, the objective of the current study was to enhance repair via application of autologous adipose derived stromal cells (ASCs) and the tenogenic growth factor bone morphogenetic protein (BMP) 12. Controlled delivery of cells and growth factor was achieved in a clinically relevant canine model using a nanofiber/fibrin-based scaffold. Control groups consisted of repair-only (no scaffold) and acellular scaffold. Repairs were evaluated after 28 days of healing using biomechanical, biochemical, and proteomics analyses. Range of motion was reduced in the groups that received scaffolds compared to normal. There was no effect of ASC+BMP12 treatment for range of motion or tensile properties outcomes versus repair-only. Biochemical assays demonstrated increased DNA, glycosaminoglycans, and crosslink concentration in all repair groups compared to normal, but no effect of ASC+BMP12. Total collagen was significantly decreased in the acellular scaffold group compared to normal and significantly increased in the ASC+BMP12 group compared to the acellular scaffold group. Proteomics analysis comparing healing tendons to uninjured tendons revealed significant increases in proteins associated with inflammation, stress response, and matrix degradation. Treatment with ASC+BMP12 amplified these unfavorable changes. In summary, the treatment approach used in this study induced a negative inflammatory reaction at the repair site leading to poor healing. Future approaches should consider cell and growth factor delivery methods that do not incite negative local reactions.