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基于细胞的疗法在动物模型中具有骨关节炎的疾病修饰作用。ESSKA 矫形生物倡议的系统评价。第 1 部分:脂肪组织来源的基于细胞的可注射疗法。

Cell-based therapies have disease-modifying effects on osteoarthritis in animal models. A systematic review by the ESSKA Orthobiologic Initiative. Part 1: adipose tissue-derived cell-based injectable therapies.

机构信息

IRCCS Istituto Ortopedico Galeazzi, Laboratorio di Biotecnologie Applicate all'Ortopedia, Milan, Italy.

Applied and Translational Research Center, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.

出版信息

Knee Surg Sports Traumatol Arthrosc. 2023 Feb;31(2):641-655. doi: 10.1007/s00167-022-07063-7. Epub 2022 Sep 14.

Abstract

PURPOSE

The aim of this systematic review was to determine if adipose tissue-derived cell-based injectable therapies can induce disease-modifying effects in joints affected by osteoarthritis (OA).

METHODS

A systematic review was performed on three electronic databases (PubMed, Web of Science, Embase) according to PRISMA guidelines. A synthesis of the results was performed investigating disease-modifying effects in preclinical studies comparing injectable adipose-derived products with OA controls or other products, different formulations or injection intervals, and the combination with other products. The risk of bias was assessed according to the SYRCLE's tool.

RESULTS

Seventy-one studies were included (2,086 animals) with an increasing publication trend over time. Expanded cells were used in 65 studies, 3 studies applied point of care products, and 3 studies investigated both approaches. Overall, 48 out of 51 studies (94%) reported better results with adipose-derived products compared to OA controls, with positive findings in 17 out of 20 studies (85%) in macroscopic, in 37 out of 40 studies (93%) in histological, and in 22 out of 23 studies (96%)  in immunohistochemical evaluations. Clinical and biomarker evaluations showed positive results in 14 studies out of 18 (78%) and 12 studies out of 14 (86%), while only 9 studies out of 17 (53%) of the imaging evaluations were able to detect differences versus controls. The risk of bias was low in 38% of items, unclear in 51%, and high in (11%).

CONCLUSION

The current preclinical models document consistent evidence of disease-modifying effects of adipose-derived cell-based therapies for the treatment of OA. The high heterogeneity of the published studies highlights the need for further targeted research to provide recommendations on the optimal methodologies for a more effective application of these injective therapies for the treatment of OA in clinical practice.

LEVEL OF EVIDENCE

II.

摘要

目的

本系统评价旨在确定脂肪组织源性细胞注射疗法是否能在骨关节炎(OA)受累关节中产生疾病修饰作用。

方法

根据 PRISMA 指南,对三个电子数据库(PubMed、Web of Science、Embase)进行了系统评价。通过比较注射脂肪衍生产品与 OA 对照或其他产品、不同配方或注射间隔以及与其他产品联合使用的临床前研究,对疾病修饰效果进行综合分析。根据 SYRCLE 工具评估偏倚风险。

结果

共纳入 71 项研究(2086 只动物),研究数量随时间呈上升趋势。有 65 项研究使用了扩增细胞,3 项研究应用了即时产品,3 项研究同时研究了这两种方法。总体而言,与 OA 对照组相比,51 项研究中有 48 项(94%)报告了脂肪衍生产品的更好结果,20 项研究中有 17 项(85%)、40 项研究中有 37 项(93%)、23 项研究中有 22 项(96%)在宏观、组织学和免疫组织化学评估中具有阳性发现。18 项临床和生物标志物评估中有 14 项(78%)和 14 项中有 12 项(86%)显示阳性结果,而 17 项影像学评估中有 9 项(53%)能够检测到与对照组的差异。38%的项目偏倚风险低,51%的项目偏倚风险不清楚,11%的项目偏倚风险高。

结论

目前的临床前模型为脂肪源性细胞治疗 OA 的疾病修饰作用提供了一致的证据。发表研究的高度异质性突出表明,需要进一步进行有针对性的研究,为这些注射疗法在临床实践中治疗 OA 的更有效应用提供最佳方法的建议。

证据水平

II。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dd6/9898370/68ba5bda6116/167_2022_7063_Fig1_HTML.jpg

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