Didamoony Manar A, Soubh Ayman A, Ahmed Lamiaa A
Pharmacology and Toxicology Department, Faculty of Pharmacy, Egyptian Russian University, Cairo, 11829, Egypt.
Pharmacology and Toxicology Department, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Giza, 12451, Egypt.
Drug Deliv Transl Res. 2025 Jan 24. doi: 10.1007/s13346-024-01784-7.
Liver fibrosis is still a serious health concern worldwide, and there is increasing interest in mesenchymal stem cells (MSCs) with tremendous potential for treating this disease because of their regenerative and paracrine effects. Recently, many researches have focused on using the released exosomes (EXOs) from stem cells to treat liver fibrosis rather than using parent stem cells themselves. MSC-derived EXOs (MSC-EXOs) have demonstrated favourable outcomes similar to cell treatment in terms of regenerative, immunomodulatory, anti-apoptotic, anti-oxidant, anti-necroptotic, anti-inflammatory and anti-fibrotic actions in several models of liver fibrosis. EXOs are superior to their parent cells in several terms, including lower immunogenicity and risk of tumour formation. However, maintaining the stability and efficacy of EXOs after in vivo transplantation remains a major challenge in their clinical applicability. Therefore, several strategies have been applied in EXOs engineering, such as parental cell modification or modifying EXOs directly to achieve optimum performance of EXOs in treating liver fibrosis. Herein, we discuss the underlying mechanisms of liver fibrosis with an overview of the available therapies, among them EXOs. We also summarise the recent developments in improving the effectiveness of EXOs with the advantages and limitations of these approaches in terms of the upcoming clinical applications.
肝纤维化在全球范围内仍是一个严重的健康问题，由于间充质干细胞（MSCs）具有再生和旁分泌作用，其在治疗该疾病方面具有巨大潜力，因此人们对其兴趣与日俱增。最近，许多研究集中在利用干细胞释放的外泌体（EXOs）来治疗肝纤维化，而不是使用干细胞本身。在几种肝纤维化模型中，间充质干细胞来源的外泌体（MSC-EXOs）在再生、免疫调节、抗凋亡、抗氧化、抗坏死性凋亡、抗炎和抗纤维化作用方面已显示出与细胞治疗相似的良好效果。外泌体在几个方面优于其亲本细胞，包括较低的免疫原性和肿瘤形成风险。然而，在体内移植后维持外泌体的稳定性和有效性仍然是其临床应用中的一个主要挑战。因此，一些策略已应用于外泌体工程，如亲本细胞修饰或直接对外泌体进行修饰，以实现外泌体在治疗肝纤维化方面的最佳性能。在此，我们讨论肝纤维化的潜在机制，并概述现有治疗方法，其中包括外泌体。我们还总结了提高外泌体有效性的最新进展，以及这些方法在即将到来的临床应用方面的优缺点。
