Hertel Fernanda Campos, Silva Aline Silvestrini da, Sabino Adriano de Paula, Valente Fabrício Luciani, Reis Emily Correna Carlo
Veterinary Department, Federal University of Viçosa, Vicosa 36570-900, Brazil.
Department of Clinical and Toxicological Analysis, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil.
Biology (Basel). 2022 May 11;11(5):733. doi: 10.3390/biology11050733.
Mesenchymal stromal cells (MSCs) have long been used in research for bone regeneration, with evidence of their beneficial properties. In the segmental area of MSC-based therapies, MSC-derived extracellular vesicles (EVs) have also shown great therapeutic effects in several diseases, including bone healing. This study aimed to assess whether the conditioning of MSCs improves the therapeutic effects of their derived extracellular vesicles for bone regeneration. Electronic research was performed until February 2021 to recover the studies in the following databases: PubMed, Scopus, and Web of Science. The studies were screened based on the inclusion criteria. Relevant information was extracted, including in vitro and in vivo experiments, and the animal studies were evaluated for risk of bias by the SYRCLE tool. A total of 463 studies were retrieved, and 18 studies met the inclusion criteria (10 studies for their in vitro analysis, and 8 studies for their in vitro and in vivo analysis). The conditioning methods reported included: osteogenic medium; dimethyloxalylglycine; dexamethasone; strontium-substituted calcium silicate; hypoxia; 3D mechanical microenvironment; and the overexpression of miR-375, bone morphogenetic protein-2, and mutant hypoxia-inducible factor-1α. The conditioning methods of MSCs in the reported studies generate exosomes able to significantly promote bone regeneration. However, heterogeneity regarding cell source, conditioning method, EV isolation and concentration, and defect model was observed among the studies. The different conditioning methods reported in this review do improve the therapeutic effects of MSC-derived EVs for bone regeneration, but they still need to be addressed in larger animal models for further clinical application.
间充质基质细胞（MSCs）长期以来一直用于骨再生研究，有证据表明它们具有有益特性。在基于MSCs的治疗领域，MSCs衍生的细胞外囊泡（EVs）在包括骨愈合在内的多种疾病中也显示出巨大的治疗效果。本研究旨在评估MSCs的预处理是否能提高其衍生的细胞外囊泡对骨再生的治疗效果。截至2021年2月进行了电子检索，以检索以下数据库中的研究：PubMed、Scopus和Web of Science。根据纳入标准对研究进行筛选。提取相关信息，包括体外和体内实验，并通过SYRCLE工具评估动物研究的偏倚风险。共检索到463项研究，18项研究符合纳入标准（10项研究进行体外分析，8项研究进行体外和体内分析）。报告的预处理方法包括：成骨培养基；二甲基草酰甘氨酸；地塞米松；锶取代硅酸钙；缺氧；三维机械微环境；以及miR-375、骨形态发生蛋白-2和突变型缺氧诱导因子-1α的过表达。报告研究中MSCs的预处理方法产生的外泌体能够显著促进骨再生。然而，研究之间在细胞来源、预处理方法、EV分离和浓度以及缺损模型方面存在异质性。本综述中报告的不同预处理方法确实提高了MSCs衍生的EVs对骨再生的治疗效果，但仍需要在更大的动物模型中进行研究以进一步用于临床应用。
