Treatment of Achilles Tendinopathy with Autologous Adipose-derived Stromal Vascular Fraction: Results of a Randomized Prospective Clinical Trial
Treatment of Achilles Tendinopathy with Autologous Adipose-derived Stromal Vascular Fraction: Results of a Randomized Prospective Clinical Trial
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DOI：
10.1177/2325967116s00128
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发表时间：
2016-07-29
影响因子：
2.6
通讯作者：
Usuelli F
中科院分区：
文献类型：
--
作者：
de Girolamo L;Grassi M;Viganò M;Orfei CP;Montrasio UA;Usuelli F
跟腱病通常发生在活动和不活动的人中。它包括早期疼痛和炎症的发展，随着纤维组织的发展和肌腱基质的退化而发展。目前的保守治疗方法不能提供持续满意的结果，特别是在活动性患者，尽管富血小板血浆(PRP)注射已被证明在许多情况下是有效的。脂肪来源的间充质干细胞(ASCs)在基质血管部分(SVF)内扩增或直接使用的治疗效果已被证明具有显著的抗炎和免疫调节作用，其介导的作用是活性因子的释放，因此在肌腱病的治疗中具有潜在的应用价值。非插入性跟腱病变(18~55 y/o)的患者被前瞻性纳入这项对照研究，随机分为两组：单一PRP注射组(GPSIII试剂盒，Biomet，美国)(n=28条)或单一脂肪组织SVF(FastKit，Corios，意大利)注射组(n=28条肌腱)。所有患者在术前、治疗后15、30、60、120、180天分别采用VAS疼痛、VISA-A、AOFAS和SF-36量表进行临床评估。治疗前、治疗后4个月和6个月分别行超声和核磁共振检查。体外分析每例患者1份SVF的间充质干细胞(MSC)含量、活性、增殖率、分化潜能和免疫调节能力。以VISA-A评分为基础进行力量分析，计算研究样本量。所有结果均以平均值±标准差表示。对配对数据进行Wilcoxon检验以比较手术前后的变量。两组患者的人群背景数据和术前评分相似(p>；0.05)。在最后一次随访时，两组患者的所有评分均较基线有显着改善(p<；0.05)。在SVF患者中，这些改善更快，在治疗后15天就已经开始的注射前水平的评分明显更高。事实上，在这个时间点上，两组之间在VAS、AOFAS和VISA-A评分方面有显著差异(P<；0.05)，其中SVF组的结果更好。6个月后，两组患者的临床体征均有不同程度的改善，但无明显差异。两组均未观察到副作用。体外分析显示，SVF标本中有少量的MSCs，但在体外炎症模型中，这些细胞能够有效地增殖和分化，并发挥良好的免疫调节作用。PRP和SVF均是治疗跟腱病变安全有效的方法。然而，SVF可以更快地取得效果，因此可以考虑这种治疗特别适合需要更早恢复体力活动的患者。
Achilles tendinopathy commonly occurs in both active and inactive persons. It consists in the development of pain and inflammation in the early phases, with progression to the development of fibrotic tissue and degeneration of tendon matrix. Current conservative treatment approaches do not provide sustained satisfactory results, particularly in active patients, although platelet rich plasma (PRP) injection have shown to be effective in many cases. The therapeutic effect of adipose-derived mesenchymal stem cells (ASCs), either expanded or used directly within the stromal vascular fraction (SVF), have demonstrated to possess significant anti-inflammatory and immunomodulatory effects, mediated by the release of active factors, and thus potentially useful in the treatment of tendinopathy. Patients affected by non-insertional Achilles tendinopathy (range 18-55 y/o) were prospectively enrolled in this controlled study, and randomly assigned either to single PRP injection group (GPSIII kit, Biomet, USA) (n=28 tendons) or single adipose tissue SVF (FastKit, Corios, Italy) (n=28 tendons) injection group. All patients were assessed clinically pre-operatively and at 15, 30, 60, 120 and 180 days from treatment, using VAS Pain, VISA-A, AOFAS and SF-36 forms. Patients also underwent to US and MRI before treatment and then at 4 and 6 month-follow-ups. An aliquot of SVF of each patient was analyzed in vitro for mesenchymal stem cells (MSC) content, viability, proliferation rate, differentiation potential and immunomodulatory ability. Sample size of the study was calculated with a power analysis based on VISA-A score. All the results are expressed as mean ± standard deviation. A Wilcoxon test for paired data was performed to compare variables before and after surgery. Population background data and pre-operative scores were similar in the two groups (p>0.05). At final follow up both patients group showed significantly improvements in all the scores in comparison to baseline (p<0.05). In SVF patients these improvements were faster, with significantly better scores with respect to pre-injection level already starting 15 days after treatment. Indeed at this time point a significant difference between groups in term of VAS, AOFAS and VISA-A score was observed (p<0.05), with better results in the SVF group. After 6 months MR and ultrasounds showed an improvement of clinical signs in both groups, without relevant differences. No side effects were observed in neither groups. In vitro analysis showed a modest content of MSCs in the SVF samples; however these cells were able to efficiently proliferate and differentiate, and to exert good immunomodulatory effect in an in vitro inflammatory model. Both PRP and SVF are safe and effective treatments for Achilles tendinopathy. However, SVF allowed to obtain faster results, thus allowing to consider this treatment particularly suitable for patients requiring to come back to physical activities sooner.