Pluronic F127 hydrogel-loaded extracellular vesicles from adipose-derived mesenchymal stem cells promote tracheal cartilage regeneration via SCNN1B delivery

IF 4.2 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Nanomedicine : nanotechnology, biology, and medicine Pub Date : 2024-04-24 DOI:10.1016/j.nano.2024.102748

Juncheng Guo PhD , Yijun Yang PhD , Yang Xiang PhD , Xueyi Guo PhD , Shufang Zhang PhD

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Abstract

Extracellular vesicles (EVs) derived from adipose-derived mesenchymal stem cells (AMSC-EVs) have been highlighted as a cell-free therapy due to their regenerative capability to enhance tissue and organ regeneration. Herein, we aimed to examine the mechanism of PF127-hydrogel@AMSC-EVs in promoting tracheal cartilage defect repair. Based on bioinformatics methods, SCNN1B was identified as a key gene for the osteogenic differentiation of AMSCs induced by AMSC-EVs. EVs were isolated from rat AMSCs and then loaded onto thermo-sensitive PF-127 hydrogel to develop PF127-hydrogel@AMSC-EVs. It was established that PF127-hydrogel@AMSC-EVs could effectively deliver SCNN1B into AMSCs, where SCNN1B promoted AMSC osteogenic differentiation. The promotive effect was evidenced by enhanced ALP activity, extracellular matrix mineralization, and expression of s-glycosaminoglycan, RUNX2, OCN, collagen II, PERK, and ATF4. Furthermore, the in vivo experiments revealed that PF127-hydrogel@AMSC-SCNN1B-EVs stimulated tracheal cartilage regeneration in rats through PERK/ATF4 signaling axis activation. Therefore, PF127-hydrogel@AMSC-SCNN1B-EVs may be a novel cell-free biomaterial to facilitate tracheal cartilage regeneration and cartilage injury repair.

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从脂肪间充质干细胞中提取的Pluronic F127水凝胶负载细胞外囊泡通过SCNN1B递送促进气管软骨再生。

从脂肪间充质干细胞（AMSC-EVs）中提取的细胞外囊泡（EVs）具有促进组织和器官再生的再生能力，因此被视为一种无细胞疗法。在此，我们旨在研究PF127-水凝胶@AMSC-EVs促进气管软骨缺损修复的机制。基于生物信息学方法，我们发现SCNN1B是AMSC-EVs诱导AMSCs成骨分化的关键基因。研究人员从大鼠AMSCs中分离出EVs，然后将其负载到热敏性PF-127水凝胶上，开发出PF127-水凝胶@AMSC-EVs。结果表明，PF127-水凝胶@AMSC-EVs能有效地将SCNN1B输送到AMSCs中，SCNN1B能促进AMSC的成骨分化。这种促进作用表现在ALP活性、细胞外基质矿化以及s-糖胺聚糖、RUNX2、OCN、胶原蛋白II、PERK和ATF4的表达增强。此外，体内实验显示，PF127-水凝胶@AMSC-SCNN1B-EVs 通过激活 PERK/ATF4 信号轴刺激大鼠气管软骨再生。因此，PF127-水凝胶@AMSC-SCNN1B-EVs可能是一种促进气管软骨再生和软骨损伤修复的新型无细胞生物材料。

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来源期刊

Nanomedicine : nanotechnology, biology, and medicine 工程技术-纳米科技

CiteScore

11.10

自引率

0.00%

发文量

133

审稿时长

42 days

期刊介绍： The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.