EVs from cells at the early stages of chondrogenesis delivered by injectable SIS dECM promote cartilage regeneration.

IF 6.7 1区 工程技术 Q1 CELL & TISSUE ENGINEERING
Journal of Tissue Engineering Pub Date : 2024-08-17 eCollection Date: 2024-01-01 DOI:10.1177/20417314241268189
Weilai Zhu, Jiaying Shi, Bowen Weng, Zhenger Zhou, Xufeng Mao, Senhao Pan, Jing Peng, Chi Zhang, Haijiao Mao, Mei Li, Jiyuan Zhao
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引用次数: 0

Abstract

Articular cartilage defect therapy is still dissatisfactory in clinic. Direct cell implantation faces challenges, such as tumorigenicity, immunogenicity, and uncontrollability. Extracellular vesicles (EVs) based cell-free therapy becomes a promising alternative approach for cartilage regeneration. Even though, EVs from different cells exhibit heterogeneous characteristics and effects. The aim of the study was to discover the functions of EVs from the cells during chondrogenesis timeline on cartilage regeneration. Here, bone marrow mesenchymal stem cells (BMSCs)-EVs, juvenile chondrocytes-EVs, and adult chondrocytes-EVs were used to represent the EVs at different differentiation stages, and fibroblast-EVs as surrounding signals were also joined to compare. Fibroblasts-EVs showed the worst effect on chondrogenesis. While juvenile chondrocyte-EVs and adult chondrocyte-EVs showed comparable effect on chondrogenic differentiation as BMSCs-EVs, BMSCs-EVs showed the best effect on cell proliferation and migration. Moreover, the amount of EVs secreted from BMSCs were much more than that from chondrocytes. An injectable decellularized extracellular matrix (dECM) hydrogel from small intestinal submucosa (SIS) was fabricated as the EVs delivery platform with natural matrix microenvironment. In a rat model, BMSCs-EVs loaded SIS hydrogel was injected into the articular cartilage defects and significantly enhanced cartilage regeneration in vivo. Furthermore, protein proteomics revealed BMSCs-EVs specifically upregulated multiple metabolic and biosynthetic processes, which might be the potential mechanism. Thus, injectable SIS hydrogel loaded with BMSCs-EVs might be a promising therapeutic way for articular cartilage defect.

通过注射 SIS dECM 从软骨形成早期阶段的细胞中提取的 EV 可促进软骨再生。
关节软骨缺损治疗在临床上仍不尽如人意。直接植入细胞面临着致瘤性、免疫原性和不可控性等挑战。基于细胞外囊泡(EVs)的无细胞疗法成为软骨再生的一种前景广阔的替代方法。尽管来自不同细胞的细胞外囊泡表现出不同的特性和作用。这项研究的目的是发现软骨生成过程中来自细胞的EVs对软骨再生的功能。本研究以骨髓间充质干细胞(BMSCs)-EVs、幼年软骨细胞-EVs和成年软骨细胞-EVs代表不同分化阶段的EVs,并加入成纤维细胞-EVs作为周围信号进行比较。成纤维细胞-EVs 对软骨形成的影响最差。幼年软骨细胞-EVs 和成年软骨细胞-EVs 对软骨分化的影响与 BMSCs-EVs 相当,而 BMSCs-EVs 对细胞增殖和迁移的影响最好。此外,BMSCs 分泌的 EVs 量远高于软骨细胞。研究人员从小肠粘膜下层(SIS)中提取了一种可注射的脱细胞细胞外基质(dECM)水凝胶,作为具有天然基质微环境的EVs递送平台。在大鼠模型中,将负载有 BMSCs-EVs 的 SIS 水凝胶注入关节软骨缺损处,可显著促进软骨在体内的再生。此外,蛋白质组学研究发现,BMSCs-EVs 能特异性地上调多种代谢和生物合成过程,这可能是其潜在的机制。因此,负载有BMSCs-EVs的可注射SIS水凝胶可能是治疗关节软骨缺损的一种很有前景的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Tissue Engineering
Journal of Tissue Engineering Engineering-Biomedical Engineering
CiteScore
11.60
自引率
4.90%
发文量
52
审稿时长
12 weeks
期刊介绍: The Journal of Tissue Engineering (JTE) is a peer-reviewed, open-access journal dedicated to scientific research in the field of tissue engineering and its clinical applications. Our journal encompasses a wide range of interests, from the fundamental aspects of stem cells and progenitor cells, including their expansion to viable numbers, to an in-depth understanding of their differentiation processes. Join us in exploring the latest advancements in tissue engineering and its clinical translation.
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