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人胎盘源细胞在肌腱损伤临床前模型中的应用。

Use of Human Placenta-Derived Cells in a Preclinical Model of Tendon Injury.

机构信息

Missouri Orthopaedic Institute, University of Missouri, Columbia, Missouri.

Sports Medicine and Shoulder Service, The Hospital for Special Surgery, New York, NY.

出版信息

J Bone Joint Surg Am. 2019 Jul 3;101(13):e61. doi: 10.2106/JBJS.15.01381.

Abstract

BACKGROUND

Emerging data suggest that human cells derived from extraembryonic tissues may have favorable musculoskeletal repair properties. The purpose of this study was to determine whether the injection of human placenta-derived mesenchymal-like stromal cells, termed placental expanded cells (PLX-PAD), would improve tendon healing in a preclinical model of tendinopathy.

METHODS

Sixty male Sprague-Dawley rats underwent bilateral patellar tendon injection with either saline solution (control) or PLX-PAD cells (2 × 10 cells/100 µL) 6 days after collagenase injection to induce tendon degeneration. Animals were killed at specific time points for biomechanical, histological, and gene expression analyses of the healing patellar tendons.

RESULTS

Biomechanical testing 2 weeks after the collagenase injury demonstrated better biomechanical properties in the tendons treated with PLX-PAD cells. The load to failure of the PLX-PAD-treated tendons was higher than that of the saline-solution-treated controls at 2 weeks (77.01 ± 10.51 versus 58.87 ± 11.97 N, p = 0.01). There was no significant difference between the 2 groups at 4 weeks. There were no differences in stiffness at either time point. Semiquantitative histological analysis demonstrated no significant differences in collagen organization or cellularity between the PLX-PAD and saline-solution-treated tendons. Gene expression analysis demonstrated higher levels of interleukin-1β (IL-1β) and IL-6 early in the healing process in the PLX-PAD-treated tendons.

CONCLUSIONS

Human placenta-derived cell therapy induced an early inflammatory response and a transient beneficial effect on tendon failure load in a model of collagenase-induced tendon degeneration.

CLINICAL RELEVANCE

Human extraembryonic tissues, such as the placenta, are an emerging source of cells for musculoskeletal repair and may hold promise as a point-of-care cell therapy for tendon injuries.

摘要

背景

新出现的数据表明,源自胚胎外组织的人类细胞可能具有良好的肌肉骨骼修复特性。本研究的目的是确定注射人胎盘衍生的间充质样基质细胞(称为胎盘扩展细胞,PLX-PAD)是否会改善肌腱病的临床前模型中的肌腱愈合。

方法

60 只雄性 Sprague-Dawley 大鼠在胶原酶注射后 6 天接受双侧髌腱注射生理盐水(对照)或 PLX-PAD 细胞(2×10 个细胞/100µL),以诱导腱变性。在特定时间点处死动物,对愈合的髌腱进行生物力学、组织学和基因表达分析。

结果

胶原酶损伤后 2 周的生物力学测试显示,PLX-PAD 细胞处理的肌腱具有更好的生物力学性能。PLX-PAD 处理的肌腱的失效负载高于生理盐水处理的对照组,在 2 周时为 77.01±10.51N 与 58.87±11.97N(p=0.01)。两组在 4 周时没有差异。在两个时间点,刚度均无差异。半定量组织学分析表明,PLX-PAD 和生理盐水处理的肌腱之间的胶原组织和细胞数量没有差异。基因表达分析表明,在 PLX-PAD 处理的肌腱中,白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)的表达在愈合过程的早期更高。

结论

人胎盘源性细胞治疗在胶原酶诱导的腱变性模型中诱导了早期炎症反应,并暂时提高了腱失效负载。

临床相关性

人胚胎外组织,如胎盘,是肌肉骨骼修复的新兴细胞来源,可能作为肌腱损伤的即时细胞治疗方法具有前景。

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