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间充质干细胞来源的外泌体和微小RNA在软骨再生中的作用:生物发生、功效、miRNA富集与递送

Mesenchymal Stem Cell-Derived Exosomes and MicroRNAs in Cartilage Regeneration: Biogenesis, Efficacy, miRNA Enrichment and Delivery.

作者信息

Foo Jhi Biau, Looi Qi Hao, How Chee Wun, Lee Sau Har, Al-Masawa Maimonah Eissa, Chong Pei Pei, Law Jia Xian

机构信息

School of Pharmacy, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya 47500, Malaysia.

Centre for Drug Discovery and Molecular Pharmacology (CDDMP), Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya 47500, Malaysia.

出版信息

Pharmaceuticals (Basel). 2021 Oct 28;14(11):1093. doi: 10.3390/ph14111093.

Abstract

Exosomes are the small extracellular vesicles secreted by cells for intercellular communication. Exosomes are rich in therapeutic cargos such as microRNA (miRNA), long non-coding RNA (lncRNA), small interfering RNA (siRNA), DNA, protein, and lipids. Recently, many studies have focused on miRNAs as a promising therapeutic factor to support cartilage regeneration. Exosomes are known to contain a substantial amount of a variety of miRNAs. miRNAs regulate the post-transcriptional gene expression by base-pairing with the target messenger RNA (mRNA), leading to gene silencing. Several exosomal miRNAs have been found to play a role in cartilage regeneration by promoting chondrocyte proliferation and matrix secretion, reducing scar tissue formation, and subsiding inflammation. The exosomal miRNA cargo can be modulated using techniques such as cell transfection and priming as well as post-secretion modifications to upregulate specific miRNAs to enhance the therapeutic effect. Exosomes are delivered to the joints through direct injection or via encapsulation within a scaffold for sustained release. To date, exosome therapy for cartilage injuries has yet to be optimized as the ideal cell source for exosomes, and the dose and method of delivery have yet to be identified. More importantly, a deeper understanding of the role of exosomal miRNAs in cartilage repair is paramount for the development of more effective exosome therapy.

摘要

外泌体是细胞分泌的用于细胞间通讯的小细胞外囊泡。外泌体富含治疗性物质,如微小RNA(miRNA)、长链非编码RNA(lncRNA)、小干扰RNA(siRNA)、DNA、蛋白质和脂质。最近,许多研究聚焦于miRNA,将其作为支持软骨再生的一种有前景的治疗因子。已知外泌体含有大量的各种miRNA。miRNA通过与靶信使RNA(mRNA)碱基配对来调节转录后基因表达,从而导致基因沉默。已发现几种外泌体miRNA通过促进软骨细胞增殖和基质分泌、减少瘢痕组织形成以及减轻炎症,在软骨再生中发挥作用。外泌体miRNA成分可通过细胞转染和预处理等技术以及分泌后修饰进行调节,以上调特定miRNA以增强治疗效果。外泌体通过直接注射或封装在支架中以实现缓释的方式递送至关节。迄今为止,由于外泌体的理想细胞来源以及递送剂量和方法尚未确定,用于软骨损伤的外泌体疗法尚未得到优化。更重要的是,深入了解外泌体miRNA在软骨修复中的作用对于开发更有效的外泌体疗法至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c735/8618513/6c2ef9efffc2/pharmaceuticals-14-01093-g001.jpg

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