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Adipose micro-grafts enhance tendinopathy healing in ovine model: An in vivo experimental perspective study
STEM CELLS Translational Medicine ( IF 5.4 ) Pub Date : 2021-08-16 , DOI: 10.1002/sctm.20-0496 Angela Palumbo Piccionello 1 , Valentina Riccio 1 , Letizia Senesi 2 , Antonella Volta 3 , Luca Pennasilico 1 , Riccardo Botto 1 , Giacomo Rossi 1 , Adolfo Maria Tambella 1 , Livio Galosi 1 , Carlotta Marini 1 , Cecilia Vullo 1 , Antonio Gigante 4 , Barbara Zavan 5 , Francesco De Francesco 2 , Michele Riccio 2
STEM CELLS Translational Medicine ( IF 5.4 ) Pub Date : 2021-08-16 , DOI: 10.1002/sctm.20-0496 Angela Palumbo Piccionello 1 , Valentina Riccio 1 , Letizia Senesi 2 , Antonella Volta 3 , Luca Pennasilico 1 , Riccardo Botto 1 , Giacomo Rossi 1 , Adolfo Maria Tambella 1 , Livio Galosi 1 , Carlotta Marini 1 , Cecilia Vullo 1 , Antonio Gigante 4 , Barbara Zavan 5 , Francesco De Francesco 2 , Michele Riccio 2
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In Europe, approximatively 100 000 to 500 000 tendon repairs are performed every year. These procedures are associated with a considerable rate of postoperative complications (from 6% to 11%). Autologous micro-grafts (AAMG) and stromal vascular fraction (SVF) have been shown to improve tendon healing in 60% to 70% of treated rodents. The purpose of this study was to evaluate the effects of AAMG in a sheep model with tendinopathy. We used sheep models because, as a large animal, they are more comparable to humans. The hypothesis was that SVF injection would improve tendon healing compared with the control group, reducing inflammatory and matrix degrading, while increasing anti-inflammatory expression and collagen synthesis in the early stage of tendon injury. Sixteen Apennine sheep aged 2 to 5 years underwent 500 UI type I collagenase injection into both common calcaneal tendons (CCT) to induce tendinopathy. After 15 days (T0), one CCT in every ovine underwent randomly to 2.5 mL of AAMG obtained by mechanical disruption and the contralateral CCTs received no treatment. Clinical, ecographic, and sonographic evaluations were performed after 4 weeks (T1) and 8 weeks (T2). Histological, immunohistochemical, real-time polymerase chain reaction (RT-PCR), and biomechanical evaluations were performed at T2. At T2, the treated group showed a final tendon diameter (9.1 ± 1.4 mm) and a hardness expression (62%) that were similar to the original healthy tendon (8.1 ± 1.1 mm; 100%), with a significant recovery compared with the control group (9.5 ± 1.7 mm; 39%). Moreover, histological analysis of the treated group revealed an improvement in the fiber orientation score, fiber edema score, infiltrative-inflammatory process, and necrosis score (4.3 ± 3.3) compared with control group (8.8 ± 2.9). Immunohistochemically, the treated group showed high expression of collagen 1, Factor VIII and significantly low expression of collagen 3. These data were confirmed by RT-PCR analysis. The study findings suggested that AAMGs obtained through mechanical disruption present a safe, efficient, and reliable technique, enhancing tendon healing.
中文翻译：
脂肪微移植物增强绵羊模型肌腱病的愈合：体内实验透视研究
在欧洲，每年大约进行 100 000 至 500 000 例肌腱修复手术。这些手术与相当高的术后并发症发生率相关（从 6% 到 11%）。自体微移植 (AAMG) 和基质血管部分 (SVF) 已被证明可以改善 60% 至 70% 的接受治疗的啮齿动物的肌腱愈合。本研究的目的是评估 AAMG 在患有肌腱病的绵羊模型中的效果。我们使用绵羊模型，因为作为一种大型动物，它们与人类更具可比性。假设与对照组相比，注射 SVF 可以改善肌腱愈合，减少炎症和基质降解，同时增加肌腱损伤早期的抗炎表达和胶原蛋白合成。对 16 只 2 至 5 岁的亚平宁羊进行了 500 UI I 型胶原酶注射到跟骨跟腱 (CCT) 中以诱发肌腱病。 15天（T0）后，每只羊的1个CCT随机接受机械破碎获得的2.5 mL AAMG，对侧CCT不接受任何处理。 4周（T1）和8周（T2）后进行临床、生态学和超声检查评估。在 T2 时进行组织学、免疫组织化学、实时聚合酶链反应 (RT-PCR) 和生物力学评估。 T2时，治疗组的最终肌腱直径（9.1±1.4毫米）和硬度表达（62％）与原始健康肌腱（8.1±1.1毫米；100％）相似，与治疗组相比有显着恢复。对照组（9.5 ± 1.7 毫米；39%）。此外，治疗组的组织学分析显示，与对照组（8.8±2.9）。免疫组织化学显示，治疗组显示出胶原蛋白1、因子VIII的高表达和胶原蛋白3的显着低表达。这些数据通过RT-PCR分析得到证实。研究结果表明，通过机械破坏获得的 AAMG 是一种安全、高效、可靠的技术，可以促进肌腱愈合。
更新日期：2021-08-16
中文翻译：
脂肪微移植物增强绵羊模型肌腱病的愈合：体内实验透视研究
在欧洲，每年大约进行 100 000 至 500 000 例肌腱修复手术。这些手术与相当高的术后并发症发生率相关（从 6% 到 11%）。自体微移植 (AAMG) 和基质血管部分 (SVF) 已被证明可以改善 60% 至 70% 的接受治疗的啮齿动物的肌腱愈合。本研究的目的是评估 AAMG 在患有肌腱病的绵羊模型中的效果。我们使用绵羊模型，因为作为一种大型动物，它们与人类更具可比性。假设与对照组相比，注射 SVF 可以改善肌腱愈合，减少炎症和基质降解，同时增加肌腱损伤早期的抗炎表达和胶原蛋白合成。对 16 只 2 至 5 岁的亚平宁羊进行了 500 UI I 型胶原酶注射到跟骨跟腱 (CCT) 中以诱发肌腱病。 15天（T0）后，每只羊的1个CCT随机接受机械破碎获得的2.5 mL AAMG，对侧CCT不接受任何处理。 4周（T1）和8周（T2）后进行临床、生态学和超声检查评估。在 T2 时进行组织学、免疫组织化学、实时聚合酶链反应 (RT-PCR) 和生物力学评估。 T2时，治疗组的最终肌腱直径（9.1±1.4毫米）和硬度表达（62％）与原始健康肌腱（8.1±1.1毫米；100％）相似，与治疗组相比有显着恢复。对照组（9.5 ± 1.7 毫米；39%）。此外，治疗组的组织学分析显示，与对照组（8.8±2.9）。免疫组织化学显示，治疗组显示出胶原蛋白1、因子VIII的高表达和胶原蛋白3的显着低表达。这些数据通过RT-PCR分析得到证实。研究结果表明，通过机械破坏获得的 AAMG 是一种安全、高效、可靠的技术，可以促进肌腱愈合。
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