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脂肪来源干细胞改善胶原酶诱导的大鼠肌腱病模型

Adipose-Derived Stem Cells Improve Collagenase-Induced Tendinopathy in a Rat Model.

作者信息

Oshita Takashi, Tobita Morikuni, Tajima Satoshi, Mizuno Hiroshi

机构信息

Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan Department of Orthopaedic Surgery, Japan Self Defense Force Hospital Yokosuka, Yokosuka, Japan.

Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan.

出版信息

Am J Sports Med. 2016 Aug;44(8):1983-9. doi: 10.1177/0363546516640750. Epub 2016 Apr 11.

DOI:10.1177/0363546516640750
PMID:27159294
Abstract

BACKGROUND

Tendinopathy is a common and highly prevalent musculoskeletal disorder characterized by repetitive activity-related pain and focal tendon tenderness. Histopathologically, tendinopathic tissue mainly shows degenerative changes. Therefore, tendinopathy is not affected by anti-inflammatory therapies. A novel approach, including a stem cell-based therapy, may be beneficial for its treatment.

PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate the effects of adipose-derived stem cells (ASCs) on tendon healing in a rat tendinopathy model. The hypothesis was that ASC transplantation would improve degeneration in collagenase-induced tendinopathy.

STUDY DESIGN

Controlled laboratory study.

METHODS

Sixteen F344/NSlc rats underwent collagenase injection into the Achilles tendon to induce tendinopathy. At 1 week after collagenase injection, 8 rats received ASCs (ASC group) and 8 received phosphate-buffered saline alone (PBS group). Animals were sacrificed at 4 or 12 weeks after ASC administration, and the degree of degeneration in each tendon was histologically evaluated according to the Bonar scale. The microstructure of healing tendons was observed by scanning electron microscopy. Reverse-transcription polymerase chain reaction (RT-PCR) was performed to measure the ratio of type III collagen messenger RNA (mRNA) to type I collagen mRNA in tendons.

RESULTS

The median Bonar scale score in the ASC and PBS groups was 2.5 and 5.33 at 4 weeks after treatment and 1.0 and 4.0 at 12 weeks after treatment, respectively. Histologically, the ASC group showed a significantly lower degree of tendon degeneration than the PBS group at both time points. In the RT-PCR analysis, the ratio of type III collagen to type I collagen was significantly lower in the ASC group than in the PBS group at 12 weeks after treatment. Moreover, this ratio decreased over time in the ASC group, whereas it increased over time in the PBS group.

CONCLUSION

The study findings demonstrate that the application of ASCs results in significant improvement in the pathological findings associated with tendinopathy and the normalization of collagen ratios within the affected tendon.

CLINICAL RELEVANCE

Subcutaneous adipose tissue can be harvested easily, and ASC administration might have the potential to rapidly treat tendinopathy.

摘要

背景

肌腱病是一种常见且高度流行的肌肉骨骼疾病,其特征为与重复性活动相关的疼痛和局部肌腱压痛。在组织病理学上,肌腱病组织主要表现为退行性改变。因此,肌腱病不受抗炎治疗的影响。一种新的方法,包括基于干细胞的治疗,可能对其治疗有益。

目的/假设:本研究的目的是评估脂肪源性干细胞(ASC)对大鼠肌腱病模型中肌腱愈合的影响。假设是ASC移植将改善胶原酶诱导的肌腱病中的退变。

研究设计

对照实验室研究。

方法

16只F344/NSlc大鼠接受胶原酶注射至跟腱以诱导肌腱病。在胶原酶注射后1周,8只大鼠接受ASC(ASC组),8只大鼠仅接受磷酸盐缓冲盐水(PBS组)。在ASC给药后4周或12周处死动物,并根据博纳尔量表对每条肌腱的退变程度进行组织学评估。通过扫描电子显微镜观察愈合肌腱的微观结构。进行逆转录聚合酶链反应(RT-PCR)以测量肌腱中III型胶原信使核糖核酸(mRNA)与I型胶原mRNA的比率。

结果

治疗后4周,ASC组和PBS组的博纳尔量表评分中位数分别为2.5和5.33;治疗后12周,分别为1.0和4.0。组织学上,在两个时间点ASC组的肌腱退变程度均显著低于PBS组。在RT-PCR分析中,治疗后12周ASC组中III型胶原与I型胶原的比率显著低于PBS组。此外,该比率在ASC组中随时间下降,而在PBS组中随时间增加。

结论

研究结果表明,ASC的应用可显著改善与肌腱病相关的病理表现,并使受累肌腱内的胶原比率正常化。

临床意义

皮下脂肪组织易于获取,ASC给药可能具有快速治疗肌腱病的潜力。

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