Fujita Yu
Department of Translational Research for Exosomes, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
Inflamm Regen. 2022 Aug 1;42(1):23. doi: 10.1186/s41232-022-00210-0.
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease that occurs due to increased fibrosis of lung tissue in response to chronic injury of the epithelium. Therapeutic options for IPF remain limited as current therapies only function to decrease disease progression. Recently, extracellular vesicles (EVs), including exosomes and microvesicles, have been recognized as paracrine communicators through the component cargo. The population of cell-specific microRNAs and proteins present in EVs can regulate gene expressions of recipient cells, resulting in modulation of biological activities. EV cargoes reflect cell types and their physiological and pathological status of donor cells. Many current researches have highlighted the functions of EVs on the epithelial phenotype and fibroproliferative response in the pathogenesis of IPF. Furthermore, some native EVs could be used as a cell-free therapeutic approach for IPF as vehicles for drug delivery, given their intrinsic biocompatibility and specific target activity. EV-based therapies have been proposed as a new potential alternative to cell-based approaches. The advantage is that EVs, depending on their source, may be less immunogenic than their parental cells, likely due to a lower abundance of transmembrane proteins such as major histocompatibility complex (MHC) proteins on the surface. In the last decade, mesenchymal stem cell (MSC)-derived EVs have been rapidly developed as therapeutic products ready for clinical trials against various diseases. Considering EV functional complexity and heterogeneity, there is an urgent need to establish refined systemic standards for manufacturing processes and regulatory requirements of these medicines. This review highlights the EV-mediated cellular crosstalk involved in IPF pathogenesis and discusses the potential for EV-based therapeutics as a novel treatment modality for IPF.
特发性肺纤维化（IPF）是一种进行性肺部疾病，其发生是由于肺组织因上皮细胞慢性损伤而纤维化增加所致。IPF的治疗选择仍然有限，因为目前的治疗方法仅能减缓疾病进展。最近，细胞外囊泡（EVs），包括外泌体和微囊泡，已被认为是通过其所含成分进行旁分泌通讯的介质。EVs中存在的细胞特异性微小RNA和蛋白质群体可调节受体细胞的基因表达，从而调节生物活性。EVs的货物反映了细胞类型及其供体细胞的生理和病理状态。目前许多研究都强调了EVs在IPF发病机制中对上皮表型和纤维增生反应的作用。此外，一些天然EVs因其固有的生物相容性和特定的靶向活性，可用作IPF的无细胞治疗方法，作为药物递送的载体。基于EVs的疗法已被提议作为基于细胞的方法的一种新的潜在替代方案。其优势在于，取决于其来源，EVs可能比其亲代细胞的免疫原性更低，这可能是由于其表面跨膜蛋白（如主要组织相容性复合体（MHC）蛋白）的丰度较低。在过去十年中，间充质干细胞（MSC）衍生的EVs已迅速发展成为可用于针对各种疾病进行临床试验的治疗产品。考虑到EVs功能的复杂性和异质性，迫切需要为这些药物的生产工艺和监管要求建立完善的系统标准。本综述重点介绍了参与IPF发病机制的EV介导的细胞间相互作用，并讨论了基于EVs的疗法作为IPF新型治疗方式的潜力。
