Wang Ziyuan, Zhong Danyang, Yan Tingting, Zheng Qiang, Zhou Enjie, Ye Zhichao, He Xiaoyan, Liu Yu, Yan Jianing, Yuan Yuyang, Wang Yifan, Cai Xiujun
Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.
Department of Cardiac Surgery, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou 310016, Zhejiang, China.
ACS Appl Mater Interfaces. 2025 Mar 26;17(12):17948-17964. doi: 10.1021/acsami.4c19748. Epub 2025 Mar 14.
Mesenchymal stem cells (MSCs) play a crucial role in regenerative medicine due to their regenerative potential. However, traditional MSC-based therapies are hindered by issues such as microvascular obstruction and low cell survival after transplantation. Exosomes derived from MSCs (MSC-Exo) provide a cell-free, nanoscale alternative, mitigating these risks and offering therapeutic potential for liver diseases. Nonetheless, the functional variability of MSCs from different sources complicates their clinical application. Stem cells derived from human exfoliated deciduous teeth (SHED) offer advantages such as ease of procurement and robust proliferative capacity, but their secretome, particularly SHED-Exo, remains underexplored in the context of liver disease therapy. This study analyzed MSC-Exo from various sources via small RNA sequencing to identify differences in microRNA profiles, aiding in the selection of optimal MSC sources for clinical use. SHED-Exo was subsequently tested in an acute liver injury model, showing notable regenerative effects, including enhanced hepatocyte proliferation, macrophage polarization, and reduced inflammation. Despite strong liver-targeting properties, the rapid hepatic clearance of SHED-Exo limits its effectiveness in chronic liver diseases. To address this challenge, a GelMA-based hydrogel was developed for in situ delivery, ensuring sustained release and enhanced antifibrotic efficacy, providing a promising strategy for chronic liver disease management.
间充质干细胞（MSCs）因其再生潜力在再生医学中发挥着关键作用。然而，传统的基于MSCs的疗法受到诸如微血管阻塞和移植后细胞存活率低等问题的阻碍。源自MSCs的外泌体（MSC-Exo）提供了一种无细胞的纳米级替代方案，减轻了这些风险，并为肝脏疾病提供了治疗潜力。尽管如此，不同来源的MSCs的功能变异性使其临床应用复杂化。源自人脱落乳牙的干细胞（SHED）具有易于获取和强大增殖能力等优势，但其分泌组，特别是SHED-Exo，在肝脏疾病治疗背景下仍未得到充分研究。本研究通过小RNA测序分析了各种来源的MSC-Exo，以确定微小RNA谱的差异，有助于选择临床使用的最佳MSC来源。随后在急性肝损伤模型中测试了SHED-Exo，显示出显著的再生作用，包括增强肝细胞增殖、巨噬细胞极化和减轻炎症。尽管SHED-Exo具有强大的肝脏靶向特性，但其在肝脏中的快速清除限制了其在慢性肝病中的有效性。为应对这一挑战，开发了一种基于GelMA的水凝胶用于原位递送，确保持续释放并增强抗纤维化疗效，为慢性肝病管理提供了一种有前景的策略。
