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脂肪源性间充质基质细胞单次病灶内注射治疗手术诱导的马浅屈肌腱核心损伤的效果:一项对照实验研究

Effect of single intralesional treatment of surgically induced equine superficial digital flexor tendon core lesions with adipose-derived mesenchymal stromal cells: a controlled experimental trial.

作者信息

Geburek Florian, Roggel Florian, van Schie Hans T M, Beineke Andreas, Estrada Roberto, Weber Kathrin, Hellige Maren, Rohn Karl, Jagodzinski Michael, Welke Bastian, Hurschler Christof, Conrad Sabine, Skutella Thomas, van de Lest Chris, van Weeren René, Stadler Peter M

机构信息

Equine Clinic, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559, Hannover, Germany.

Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 112, 3584 CM, Utrecht, The Netherlands.

出版信息

Stem Cell Res Ther. 2017 Jun 5;8(1):129. doi: 10.1186/s13287-017-0564-8.

Abstract

BACKGROUND

Adipose tissue is a promising source of mesenchymal stromal cells (MSCs) for the treatment of tendon disease. The goal of this study was to assess the effect of a single intralesional implantation of adipose tissue-derived mesenchymal stromal cells (AT-MSCs) on artificial lesions in equine superficial digital flexor tendons (SDFTs).

METHODS

During this randomized, controlled, blinded experimental study, either autologous cultured AT-MSCs suspended in autologous inactivated serum (AT-MSC-serum) or autologous inactivated serum (serum) were injected intralesionally 2 weeks after surgical creation of centrally located SDFT lesions in both forelimbs of nine horses. Healing was assessed clinically and with ultrasound (standard B-mode and ultrasound tissue characterization) at regular intervals over 24 weeks. After euthanasia of the horses the SDFTs were examined histologically, biochemically and by means of biomechanical testing.

RESULTS

AT-MSC implantation did not substantially influence clinical and ultrasonographic parameters. Histology, biochemical and biomechanical characteristics of the repair tissue did not differ significantly between treatment modalities after 24 weeks. Compared with macroscopically normal tendon tissue, the content of the mature collagen crosslink hydroxylysylpyridinoline did not differ after AT-MSC-serum treatment (p = 0.074) while it was significantly lower (p = 0.027) in lesions treated with serum alone. Stress at failure (p = 0.048) and the modulus of elasticity (p = 0.001) were significantly lower after AT-MSC-serum treatment than in normal tendon tissue.

CONCLUSIONS

The effect of a single intralesional injection of cultured AT-MSCs suspended in autologous inactivated serum was not superior to treatment of surgically created SDFT lesions with autologous inactivated serum alone in a surgical model of tendinopathy over an observation period of 22 weeks. AT-MSC treatment might have a positive influence on collagen crosslinking of remodelling scar tissue. Controlled long-term studies including naturally occurring tendinopathies are necessary to verify the effects of AT-MSCs on tendon disease.

摘要

背景

脂肪组织是用于治疗肌腱疾病的间充质基质细胞(MSCs)的一个有前景的来源。本研究的目的是评估单次病灶内植入脂肪组织来源的间充质基质细胞(AT-MSCs)对马浅屈肌腱(SDFTs)人工损伤的影响。

方法

在这项随机、对照、双盲实验研究中,在9匹马的双前肢手术创建位于中心的SDFT损伤2周后,将悬浮于自体灭活血清中的自体培养AT-MSCs(AT-MSC-血清)或自体灭活血清(血清)病灶内注射。在24周内定期通过临床检查和超声(标准B模式和超声组织特征分析)评估愈合情况。马安乐死后,对SDFTs进行组织学、生化和生物力学测试检查。

结果

AT-MSC植入对临床和超声参数没有实质性影响。24周后,不同治疗方式下修复组织的组织学、生化和生物力学特征没有显著差异。与宏观正常的肌腱组织相比,AT-MSC-血清治疗后成熟胶原交联物羟赖氨酸吡啶诺林的含量没有差异(p = 0.074),而单独用血清治疗的损伤中该含量显著更低(p = 0.027)。AT-MSC-血清治疗后,破坏应力(p = 0.048)和弹性模量(p = 0.001)显著低于正常肌腱组织。

结论

在肌腱病手术模型中,在22周的观察期内,单次病灶内注射悬浮于自体灭活血清中的培养AT-MSCs的效果并不优于单独用自体灭活血清治疗手术创建的SDFT损伤。AT-MSC治疗可能对重塑瘢痕组织的胶原交联有积极影响。需要进行包括自然发生的肌腱病的对照长期研究来验证AT-MSCs对肌腱疾病的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd05/5460527/353ae139c1da/13287_2017_564_Fig1_HTML.jpg

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