Cell-based therapies have disease-modifying effects on osteoarthritis in animal models: A systematic review by the ESSKA Orthobiologic Initiative. Part 3: Umbilical cord, placenta, and other sources for cell-based injectable therapies

IF 5 2区医学 Q1 ORTHOPEDICS Knee Surgery, Sports Traumatology, Arthroscopy Pub Date : 2024-09-20 DOI:10.1002/ksa.12472

Yosef Sourugeon, Angelo Boffa, Carlotta Perucca Orfei, Laura de Girolamo, Jeremy Magalon, Mikel Sánchez, Thomas Tischer, Giuseppe Filardo, Lior Laver

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Abstract

Purpose

This systematic review aimed to investigate in animal models the presence of disease-modifying effects driven by non-bone marrow-derived and non-adipose-derived products, with a particular focus on umbilical cord and placenta-derived cell-based therapies for the intra-articular injective treatment of osteoarthritis (OA).

Methods

A systematic review was performed on three electronic databases (PubMed, Web of Science and Embase) according to PRISMA guidelines. The results were synthesised to investigate disease-modifying effects in preclinical animal studies comparing injectable umbilical cord, placenta, and other sources-derived products with OA controls. The risk of bias was assessed using the SYRCLE tool.

Results

A total of 80 studies were included (2314 animals). Cell therapies were most commonly obtained from the umbilical cord in 33 studies and placenta/amniotic tissue in 18. Cell products were xenogeneic in 61 studies and allogeneic in the remaining 19 studies. Overall, 25/27 (92.6%) of studies on umbilical cord-derived products documented better results compared to OA controls in at least one of the following outcomes: macroscopic, histological and/or immunohistochemical findings, with 19/22 of studies (83.4%) show positive results at the cartilage level and 4/6 of studies (66.7%) at the synovial level. Placenta-derived injectable products documented positive results in 13/16 (81.3%) of the studies, 12/15 (80.0%) at the cartilage level, and 2/4 (50.0%) at the synovial level, but 2/16 studies (12.5%) found overall worse results than OA controls. Other sources (embryonic, synovial, peripheral blood, dental pulp, cartilage, meniscus and muscle-derived products) were investigated in fewer preclinical studies. The risk of bias was low in 42% of items, unclear in 49%, and high in 9% of items.

Conclusion

Interest in cell-based injectable therapies for OA treatment is soaring, particularly for alternatives to bone marrow and adipose tissue. While expanded umbilical cord mesenchymal stem cells reported auspicious disease-modifying effects in preventing OA progression in animal models, placenta/amniotic tissue also reported deleterious effects on OA joints. Lower evidence has been found for other cellular sources such as embryonic, synovial, peripheral blood, dental-pulp, cartilage, meniscus, and muscle-derived products.

Level of Evidence

Level II.

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细胞疗法在动物模型中对骨关节炎具有疾病调节作用：ESSKA骨生物学计划的系统回顾。第 3 部分：脐带、胎盘和其他来源的细胞注射疗法。

目的：本系统综述旨在研究非骨髓来源和非脂肪来源产品在动物模型中的疾病调节作用，尤其关注基于脐带和胎盘来源细胞的关节内注射治疗骨关节炎（OA）疗法：根据 PRISMA 指南，在三个电子数据库（PubMed、Web of Science 和 Embase）中进行了系统性综述。综述了临床前动物研究的结果，比较了注射用脐带、胎盘和其他来源产品与OA对照组的疾病调节效果。使用SYRCLE工具对偏倚风险进行了评估：结果：共纳入 80 项研究（2314 只动物）。在33项研究中，细胞疗法最常见的来源是脐带，在18项研究中，细胞疗法最常见的来源是胎盘/羊膜组织。61项研究的细胞产品为异种，其余19项研究的细胞产品为异体。总体而言，25/27（92.6%）项关于脐带衍生产品的研究记录了与 OA 对照组相比在以下至少一项结果上更好的结果：宏观、组织学和/或免疫组化结果，其中 19/22 项研究（83.4%）在软骨水平上显示了积极的结果，4/6 项研究（66.7%）在滑膜水平上显示了积极的结果。在 13/16 项研究（81.3%）中，有 12/15 项研究（80.0%）在软骨水平和 2/4 项研究（50.0%）在滑膜水平发现了阳性结果，但有 2/16 项研究（12.5%）发现总体结果不如 OA 对照组。其他来源（胚胎、滑膜、外周血、牙髓、软骨、半月板和肌肉衍生产品）的临床前研究较少。42%的项目存在低偏倚风险，49%的项目存在不明确偏倚风险，9%的项目存在高偏倚风险：结论：人们对以细胞为基础的注射疗法治疗OA的兴趣与日俱增，尤其是骨髓和脂肪组织的替代品。据报道，扩增的脐带间充质干细胞在防止动物模型中的OA进展方面具有良好的疾病调节作用，但胎盘/羊膜组织对OA关节也有有害影响。其他细胞来源，如胚胎、滑膜、外周血、牙髓、软骨、半月板和肌肉衍生产品的证据较少：证据等级：二级。

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来源期刊

Knee Surgery, Sports Traumatology, Arthroscopy 医学-外科

CiteScore

8.10

自引率

18.40%

发文量

418

审稿时长

2 months

期刊介绍： Few other areas of orthopedic surgery and traumatology have undergone such a dramatic evolution in the last 10 years as knee surgery, arthroscopy and sports traumatology. Ranked among the top 33% of journals in both Orthopedics and Sports Sciences, the goal of this European journal is to publish papers about innovative knee surgery, sports trauma surgery and arthroscopy. Each issue features a series of peer-reviewed articles that deal with diagnosis and management and with basic research. Each issue also contains at least one review article about an important clinical problem. Case presentations or short notes about technical innovations are also accepted for publication. The articles cover all aspects of knee surgery and all types of sports trauma; in addition, epidemiology, diagnosis, treatment and prevention, and all types of arthroscopy (not only the knee but also the shoulder, elbow, wrist, hip, ankle, etc.) are addressed. Articles on new diagnostic techniques such as MRI and ultrasound and high-quality articles about the biomechanics of joints, muscles and tendons are included. Although this is largely a clinical journal, it is also open to basic research with clinical relevance. Because the journal is supported by a distinguished European Editorial Board, assisted by an international Advisory Board, you can be assured that the journal maintains the highest standards. Official Clinical Journal of the European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA).