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移植骨髓细胞在小鼠肩袖肌肉脂肪变性发展中的作用。

Role of transplanted bone marrow cells in development of rotator cuff muscle fatty degeneration in mice.

机构信息

Department of Orthopaedics and Rehabilitation, Penn State College of Medicine Milton S. Hershey Medical Center, Hershey, PA, USA.

Department of Orthopaedics and Rehabilitation, Penn State College of Medicine Milton S. Hershey Medical Center, Hershey, PA, USA.

出版信息

J Shoulder Elbow Surg. 2017 Dec;26(12):2177-2186. doi: 10.1016/j.jse.2017.06.032. Epub 2017 Aug 30.

Abstract

BACKGROUND

Rotator cuff muscle fatty degeneration after a chronic tendon tear is an irreversible pathologic change associated with poor clinical outcomes of tendon repair, and its exact pathogenesis remains unknown. We sought to investigate the role of transplanted bone marrow cells in the development of fatty degeneration, specifically in adipocyte accumulation, using a mouse model.

METHODS

Fourteen mice were divided into 2 bone marrow chimeric animal groups: bone marrow transplantation (BMT) group and reverse BMT group. For the BMT group, C57BL/6J wild-type mice underwent whole body irradiation followed by BMT into the retro-orbital sinus from green fluorescent protein (GFP)-transgenic donor mice. For the reverse BMT group, GFP-transgenic mice received BMT from C57BL/6J wild-type donor mice after irradiation. The supraspinatus tendon, infraspinatus tendon, and suprascapular nerve were surgically transected 3 weeks after transplantation. The rotator cuff muscles were harvested 13 weeks after transplantation for histologic analysis and GFP immunohistochemistry.

RESULTS

On histologic examination, both groups showed substantial fatty degeneration, fibrosis, and atrophy of the cuff muscles. The BMT group showed no noticeable GFP immunostaining, whereas the reverse BMT group showed significantly stronger GFP staining in most adipocytes (P < .001). However, both groups also showed that a small number of adipocytes originated from transplanted bone marrow cells. A small number of myocytes showed a large cytoplasmic lipid vacuole resembling adipocytes.

CONCLUSIONS

This study's findings suggest that most adipocytes in fatty degeneration of the rotator cuff muscles originate from sources other than bone marrow-derived stem cells, and there may be more than 1 source for the adipocytes.

摘要

背景

慢性肌腱撕裂后肩袖肌肉脂肪变性是一种不可逆转的病理改变,与肌腱修复的临床结果不佳有关,其确切发病机制尚不清楚。我们试图通过建立一个小鼠模型来研究移植骨髓细胞在脂肪变性发展中的作用,特别是在脂肪细胞堆积方面。

方法

14 只小鼠被分为 2 个骨髓嵌合动物组:骨髓移植(BMT)组和反向 BMT 组。对于 BMT 组,C57BL/6J 野生型小鼠接受全身照射,然后通过绿色荧光蛋白(GFP)转基因供体小鼠的眶后窦进行 BMT。对于反向 BMT 组,GFP 转基因小鼠在照射后接受来自 C57BL/6J 野生型供体小鼠的 BMT。移植后 3 周手术横断冈上肌腱、冈下肌腱和肩胛上神经。移植后 13 周取肩袖肌肉进行组织学分析和 GFP 免疫组化。

结果

组织学检查两组均显示肩袖肌肉有明显的脂肪变性、纤维化和萎缩。BMT 组未见明显 GFP 免疫染色,而反向 BMT 组大多数脂肪细胞中 GFP 染色明显增强(P <.001)。然而,两组也显示出少量脂肪细胞来源于移植的骨髓细胞。少数肌细胞表现出大的细胞质脂滴,类似于脂肪细胞。

结论

本研究结果表明,肩袖肌肉脂肪变性中的大多数脂肪细胞并非来源于骨髓源性干细胞,可能有不止 1 个来源。

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