Leal Andrés Felipe, Pachajoa Harry, Tomatsu Shunji
Centro de Investigaciones en Anomalías Congénitas y Enfermedades Raras, Universidad Icesi, Cali 760031, Colombia.
Centro de Investigaciones Clínicas, Fundación Valle de Lili, Cali 760001, Colombia.
Int J Mol Sci. 2025 Jul 4;26(13):6448. doi: 10.3390/ijms26136448.
Lysosomal storage disorders (LSDs) constitute a group of monogenic systemic diseases resulting from deficiencies in specific lysosomal enzymes that cause the intralysosomal accumulation of non- or partially degraded substrates, leading to lysosomal dysfunction. In some cases of LSDs, the bone is more severely affected, thus producing skeletal manifestations in patients. Current therapies, such as enzyme replacement therapy (ERT) and gene therapy (GT), show limited efficacy in correcting skeletal abnormalities. Increasing evidence suggests that microenvironmental disturbances also contribute significantly to disease pathogenesis. Therefore, therapeutic strategies targeting lysosomal dysfunction and microenvironmental dysregulation are needed. Mesenchymal stem-cell-derived extracellular vesicles (MSC-EVs) are emerging as promising candidates in regenerative medicine due to their immunomodulatory, pro-regenerative, and paracrine properties. MSC-EVs have shown potential to modulate the microenvironment and favor tissue repair in bone-related disorders such as osteoarthritis and osteoporosis. Interestingly, MSC-EVs can be engineered to reach the bone and carry therapeutics, including ERT- and GT-related molecules, enabling targeted delivery to hard-to-reach bone regions. This review describes the main features of MSC-EVs and discusses the therapeutic potential of MSC-EVs as a potential cell-free strategy for bone-affected LSDs.
溶酶体贮积症（LSDs）是一组单基因系统性疾病，由特定溶酶体酶的缺陷导致非降解或部分降解底物在溶酶体内蓄积，进而引起溶酶体功能障碍。在某些LSDs病例中，骨骼受影响更为严重，从而使患者出现骨骼表现。目前的治疗方法，如酶替代疗法（ERT）和基因疗法（GT），在纠正骨骼异常方面疗效有限。越来越多的证据表明，微环境紊乱在疾病发病机制中也起重要作用。因此，需要针对溶酶体功能障碍和微环境失调的治疗策略。间充质干细胞衍生的细胞外囊泡（MSC-EVs）因其免疫调节、促再生和旁分泌特性，在再生医学中成为有前景的候选物。MSC-EVs已显示出调节微环境和促进骨相关疾病（如骨关节炎和骨质疏松症）组织修复的潜力。有趣的是，MSC-EVs可经改造到达骨骼并携带治疗药物，包括与ERT和GT相关的分子，从而实现向难以到达的骨区域的靶向递送。本综述描述了MSC-EVs的主要特征，并讨论了MSC-EVs作为一种潜在的无细胞策略用于治疗骨骼受累的LSDs的治疗潜力。
