ABSTRACT

Traumatic musculoskeletal injuries are common in both the civilian and combat care settings. Significant barriers exist to repairing these injuries including fracture nonunion, muscle fibrosis, re-innervation, and compartment syndrome, as well as infection and inflammation. Recently, extracellular vesicles (EVs), including exosomes and microvesicles, have attracted attention in the field of musculoskeletal regeneration. These vesicles are released by different cell types and play a vital role in cell communication by delivering functional cargoes such as proteins and RNAs. Many of these cargo molecules can be utilized for repair purposes in skeletal disorders such as osteoporosis, osteogenesis imperfecta, sarcopenia, and fracture healing. There are, however, some challenges to overcome in order to advance the successful application of these vesicles in the therapeutic setting. These include large-scale production and isolation of exosomes, long-term storage, in vivo stability, and strategies for tissue-specific targeting and delivery. This paper reviews the general characteristics of exosomes along with their physiological roles and contribution to the pathogenesis of musculoskeletal diseases. We also highlight new findings on the use of synthetic exosomes to overcome the limitations of native exosomes in treating musculoskeletal injuries and disorders.

摘要

外伤性肌肉骨骼损伤在平民和战斗护理环境中都很常见。修复这些损伤存在重大障碍，包括骨折不愈合、肌肉纤维化、神经再支配和筋膜室综合征，以及感染和炎症。最近，细胞外囊泡（EVs），包括外泌体和微囊泡，在肌肉骨骼再生领域引起了人们的关注。这些囊泡由不同的细胞类型释放，并通过传递蛋白质和 RNA 等功能性货物在细胞通讯中发挥重要作用。许多这些货物分子可用于骨骼疾病的修复目的，例如骨质疏松症、成骨不全症、肌肉减少症和骨折愈合。然而，有 为了推进这些囊泡在治疗环境中的成功应用，需要克服一些挑战。这些包括外泌体的大规模生产和分离、长期储存、体内稳定性，以及组织特异性靶向和递送策略。本文综述了外泌体的一般特征及其生理作用和对肌肉骨骼疾病发病机制的贡献。我们还强调了使用合成外泌体克服天然外泌体在治疗肌肉骨骼损伤和疾病方面的局限性的新发现。