Sandoval Aaron Gabriel W, Badiavas Evangelos V
Harvard Medical School, Boston, MA 02115, USA.
Aegle Therapeutics, Woburn, MA 01801, USA.
Bioengineering (Basel). 2025 May 27;12(6):574. doi: 10.3390/bioengineering12060574.
Epidermolysis bullosa (EB) is a debilitating genetic skin disorder characterized by extreme fragility, chronic wounds, and severe complications, particularly in its most severe form, recessive dystrophic EB (RDEB). Current treatments focus on symptomatic relief through wound care and pain management, with recent FDA approvals of Vyjuvek and Filsuvez providing new but limited therapeutic options. However, emerging research highlights the potential of extracellular vesicles (EVs) derived from mesenchymal stem cells as a promising approach to address both the symptoms and underlying pathology of EB. EVs function as carriers of bioactive molecules, modulating inflammation, promoting tissue regeneration, and even delivering functional type VII collagen to RDEB patient cells. Unlike whole-cell therapies, EVs are non-immunogenic, have greater stability, and avoid risks such as graft-versus-host disease or tumorigenic transformation. Additionally, EVs offer diverse administration routes, including topical application, local injection, and intravenous delivery, which could extend their therapeutic reach beyond skin lesions to systemic manifestations of EB. However, challenges remain, including standardization of EV production, scalability, and ensuring consistent therapeutic potency. Despite these hurdles, EV-based therapies represent a transformative step toward addressing the complex pathology of EB, with the potential to improve wound healing, reduce fibrosis, and enhance patient quality of life.
大疱性表皮松解症（EB）是一种使人衰弱的遗传性皮肤病，其特征为皮肤极度脆弱、慢性伤口以及严重并发症，尤其是在其最严重的形式——隐性营养不良性EB（RDEB）中。目前的治疗重点是通过伤口护理和疼痛管理来缓解症状，美国食品药品监督管理局（FDA）最近批准的Vyjuvek和Filsuvez提供了新的但有限的治疗选择。然而，新出现的研究突出了源自间充质干细胞的细胞外囊泡（EVs）作为一种有前景的方法来解决EB症状和潜在病理问题的潜力。EVs作为生物活性分子的载体，调节炎症、促进组织再生，甚至将功能性VII型胶原蛋白递送至RDEB患者细胞。与全细胞疗法不同，EVs无免疫原性，具有更高的稳定性，并且避免了移植物抗宿主病或致瘤转化等风险。此外，EVs提供多种给药途径，包括局部应用、局部注射和静脉给药，这可以将其治疗范围从皮肤病变扩展到EB的全身表现。然而，挑战依然存在，包括EV生产的标准化、可扩展性以及确保一致的治疗效力。尽管存在这些障碍，基于EV的疗法代表了朝着解决EB复杂病理迈出的变革性一步，有可能改善伤口愈合、减少纤维化并提高患者生活质量。
