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利用人真皮成纤维细胞促进肩袖肌腱愈合:慢性肩袖撕裂兔模型的组织学和生物力学分析。

Rotator Cuff Tendon Healing Using Human Dermal Fibroblasts: Histological and Biomechanical Analyses in a Rabbit Model of Chronic Rotator Cuff Tears.

机构信息

Cutigen Research Institute, Tego Science, Seoul, Republic of Korea.

Department of Orthopedic Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.

出版信息

Am J Sports Med. 2021 Nov;49(13):3669-3679. doi: 10.1177/03635465211041102. Epub 2021 Sep 23.

Abstract

BACKGROUND

Tenocytes derived from tendons have been reported to be effective in the treatment of rotator cuff tears through the expression of extracellular matrix proteins. Human dermal fibroblasts, known to express collagen types I and III as tenocytes do, may likely be substitutes for tenocytes to enhance healing rotator cuff tears.

PURPOSE

To demonstrate the capability of human dermal fibroblasts to enhance healing of rotator cuff tears.

STUDY DESIGN

Controlled laboratory study.

METHODS

The cellular properties and expression profiles of growth factors were compared between human dermal fibroblasts and tenocytes. In both cell types, a series of extracellular matrix proteins were analyzed along with matrix metalloproteinases and tissue inhibitors of metalloproteinases involved in the collagenolytic system. A total of 35 rabbits were divided into 5 groups: normal (n = 2), saline control (n = 9), fibrin control (n = 9), low dose of human fibroblasts (HF-LD; n = 9), and high dose of human fibroblasts (HF-HD; n = 6). Cells were injected into the sutured lesions at 6 weeks after creation of bilateral rotator cuff tears, followed by histological and biomechanical analyses at 12 weeks.

RESULTS

Human dermal fibroblasts exhibited a protein expression pattern similar to that of tenocytes. More specifically, the expression levels of collagen types I and III were comparable between fibroblasts and tenocytes. The histological analysis of 30 surviving rabbits showed that collagen fibers were more continuous and better oriented with a more mature interface between the tendon and bone in the sutured lesions in the HF-LD and HF-HD groups. Most importantly, biomechanical strength, measured using the load to failure at the injection site, was 58.8 ± 8.9 N/kg in the HF-HD group, increasing by approximately 2-fold ( = .0003) over the saline control group.

CONCLUSION

Human dermal fibroblasts, showing cellular properties comparable with tenocytes, effectively enhanced healing of chronic rotator cuff tears in rabbits.

CLINICAL RELEVANCE

Human dermal fibroblasts can be used in place of tenocytes to enhance healing of rotator cuff tears.

摘要

背景

肌腱来源的肌腱细胞已被报道通过表达细胞外基质蛋白对肩袖撕裂治疗有效。已知与人肌腱细胞一样表达 I 型和 III 型胶原的人真皮成纤维细胞,可能是替代肌腱细胞增强肩袖撕裂愈合的替代物。

目的

证明人真皮成纤维细胞增强肩袖撕裂愈合的能力。

研究设计

对照实验室研究。

方法

比较了人真皮成纤维细胞和肌腱细胞的细胞特性和生长因子表达谱。在这两种细胞类型中,都分析了一系列细胞外基质蛋白,以及参与胶原溶解系统的基质金属蛋白酶和金属蛋白酶组织抑制剂。35 只兔子分为 5 组:正常组(n = 2)、盐水对照组(n = 9)、纤维蛋白对照组(n = 9)、低剂量人成纤维细胞组(HF-LD;n = 9)和高剂量人成纤维细胞组(HF-HD;n = 6)。在双侧肩袖撕裂形成 6 周后,将细胞注射到缝合损伤部位,然后在 12 周时进行组织学和生物力学分析。

结果

人真皮成纤维细胞表现出与肌腱细胞相似的蛋白表达模式。更具体地说,I 型和 III 型胶原的表达水平在成纤维细胞和肌腱细胞之间相当。30 只存活兔子的组织学分析表明,在 HF-LD 和 HF-HD 组的缝合损伤处,胶原纤维更加连续,定向更好,肌腱和骨骼之间的界面更加成熟。最重要的是,使用注射部位失效时的负载测量的生物力学强度,HF-HD 组为 58.8 ± 8.9 N/kg,比盐水对照组增加约 2 倍(=.0003)。

结论

具有与人肌腱细胞相当的细胞特性的人真皮成纤维细胞可有效增强兔慢性肩袖撕裂的愈合。

临床相关性

人真皮成纤维细胞可替代肌腱细胞增强肩袖撕裂的愈合。

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