Therapeutic potential and mechanisms of mesenchymal stem cell-derived exosomes as bioactive materials in tendon-bone healing.
Therapeutic potential and mechanisms of mesenchymal stem cell-derived exosomes as bioactive materials in tendon-bone healing.
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间充质干细胞来源的外泌体作为生物活性材料在肌腱-骨愈合中的治疗潜力和机制。
DOI：
10.1186/s12951-023-01778-6
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发表时间：
2023-01-16
影响因子：
10.2
通讯作者：
Wu, Haobo
中科院分区：
文献类型：
--
作者：
Zou, Jiaxuan;Yang, Weinan;Cui, Wushi;Li, Congsun;Ma, Chiyuan;Ji, Xiaoxiao;Hong, Jianqiao;Qu, Zihao;Chen, Jing;Liu, An;Wu, Haobo
关键词：
肌腱-骨止损（TBI）损伤，如前交叉韧带损伤和肩袖损伤，是最常见的软组织损伤。在大多数情况下，手术肌腱/韧带重建是治疗这类损伤所必需的。然而，相当数量的病例失败，因为髋端愈合是通过瘢痕组织形成而不是过渡组织的再生。近年来，间充质干细胞（MSCs）的治疗潜力在动物和临床研究中得到了很好的证明，如慢性截瘫、非缺血性心力衰竭和膝关节骨关节炎。间充质干细胞是一种多能干细胞，具有自我再生能力，能够分化为多种细胞，如软骨细胞、成骨细胞和脂肪细胞。大量研究表明MSCs可以促进血管生成和细胞增殖，减少炎症，并产生大量参与修复的生物活性分子。这些作用可能是由MSCs的旁分泌机制介导的，特别是通过外泌体的释放。外泌体是具有脂质双分子层和膜结构的纳米级细胞外囊泡（ev），由各种细胞类型自然释放。它们通过在细胞间传递生物活性脂质、蛋白质和核酸（如mrna和mirna）来影响受体细胞的生理和病理过程，在细胞间通讯中发挥重要作用。外泌体已被证明促进组织修复和再生。在此，我们讨论了msc来源的外泌体在TBI损伤中的应用前景。我们还回顾了msc - ev的作用及其促进肌腱-骨愈合的潜在机制。最后，讨论了当前面临的挑战和未来的研究方向。
Tendon–bone insertion (TBI) injuries, such as anterior cruciate ligament injury and rotator cuff injury, are the most common soft tissue injuries. In most situations, surgical tendon/ligament reconstruction is necessary for treating such injuries. However, a significant number of cases failed because healing of the enthesis occurs through scar tissue formation rather than the regeneration of transitional tissue. In recent years, the therapeutic potential of mesenchymal stem cells (MSCs) has been well documented in animal and clinical studies, such as chronic paraplegia, non-ischemic heart failure, and osteoarthritis of the knee. MSCs are multipotent stem cells, which have self-renewability and the ability to differentiate into a wide variety of cells such as chondrocytes, osteoblasts, and adipocytes. Numerous studies have suggested that MSCs could promote angiogenesis and cell proliferation, reduce inflammation, and produce a large number of bioactive molecules involved in the repair. These effects are likely mediated by the paracrine mechanisms of MSCs, particularly through the release of exosomes. Exosomes, nano-sized extracellular vesicles (EVs) with a lipid bilayer and a membrane structure, are naturally released by various cell types. They play an essential role in intercellular communication by transferring bioactive lipids, proteins, and nucleic acids, such as mRNAs and miRNAs, between cells to influence the physiological and pathological processes of recipient cells. Exosomes have been shown to facilitate tissue repair and regeneration. Herein, we discuss the prospective applications of MSC-derived exosomes in TBI injuries. We also review the roles of MSC–EVs and the underlying mechanisms of their effects on promoting tendon–bone healing. At last, we discuss the present challenges and future research directions.
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