Cell-Free Osteoarthritis Treatment with Sustained-Release of Chondrocyte-Targeting Exosomes from Umbilical Cord-Derived Mesenchymal Stem Cells to Rejuvenate Aging Chondrocytes

IF 16 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
ACS Nano Pub Date : 2023-07-13 DOI:10.1021/acsnano.3c01612
Hongfu Cao, Manyu Chen, Xiaolin Cui, Yuan Liu, Yuhan Liu, Siyan Deng, Tun Yuan, Yujiang Fan*, Qiguang Wang* and Xingdong Zhang, 
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引用次数: 7

Abstract

As chondrocytes from osteoarthritic cartilage usually exhibit aging and senescent characteristics, targeting aging chondrocytes could be a potential therapeutic strategy. In this study, exosomes derived from umbilical cord-derived mesenchymal stem cells (UCMSC-EXOs) combined with the chondrocyte-targeting capacity and controlled-release system were proposed for osteoarthritis (OA) treatment via rejuvenating aging chondrocytes. The essential functional miRNAs within UCMSC-EXOs were investigated, with the p53 signaling pathway identified as the key factor. To improve the therapeutic efficiency and retention time of UCMSC-EXOs in vivo, the exosomes (EXOs) were engineered on membranes with a designed chondrocyte-targeting polymers, and encapsulated within thiolated hyaluronic acid microgels to form a “two-phase” releasing system, which synergistically facilitated the repair of OA cartilage in a rat model. Together, this study highlighted the rejuvenating effects of UCMSC-EXOs on OA chondrocytes and the potential to combine with chondrocyte-targeting and sustained-release strategies toward a future cell-free OA treatment.

Abstract Image

从脐带来源的间充质干细胞中持续释放软骨细胞靶向外泌体以使老化的软骨细胞恢复活力,从而治疗无细胞骨关节炎
由于骨关节炎软骨的软骨细胞通常表现出衰老和衰老的特征,靶向老化的软骨细胞可能是一种潜在的治疗策略。在这项研究中,来自脐带间充质干细胞(UCMSC-EXOs)的外泌体结合软骨细胞靶向能力和控制释放系统,通过使老化的软骨细胞恢复活力来治疗骨关节炎(OA)。我们研究了ucmsc - exo中的基本功能mirna,并确定p53信号通路为关键因素。为了提高UCMSC-EXOs在体内的治疗效率和保留时间,将EXOs用一种设计的软骨细胞靶向聚合物修饰在膜上,并将其包裹在硫代透明质酸微凝胶中形成“两相”释放系统,协同促进大鼠OA软骨模型的修复。总之,这项研究强调了UCMSC-EXOs对OA软骨细胞的恢复作用,以及与软骨细胞靶向和缓释策略结合的潜力,以实现未来无细胞OA治疗。
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来源期刊
ACS Nano
ACS Nano 工程技术-材料科学:综合
CiteScore
26.00
自引率
4.10%
发文量
1627
审稿时长
1.7 months
期刊介绍: ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.
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