Abstract

Exosomes are the most researched extracellular vesicles. In many biological, physiological, and pathological studies, they have been identified as suitable candidates for treatment and diagnosis of diseases by acting as the carriers of both drugs and genes. Considerable success has been achieved regarding the use of exosomes for tissue regeneration, cancer diagnosis, and targeted drug/gene delivery to specific tissues. While major progress has been made in exosome extraction and purification, extraction of large quantities of exosomes is still a major challenge. This issue limits the scope of both exosome-based research and therapeutic development. In this review, we have aimed to summarize experimental studies focused at increasing the number of exosomes. Biotechnological studies aimed at identifying the pathways of exosome biogenesis to manipulate some genes in order to increase the production of exosomes. Generally, two major strategies are employed to increase the production of exosomes. First, oogenesis pathways are genetically manipulated to overexpress activator genes of exosome biogenesis and downregulate the genes involved in exosome recycling pathways. Second, manipulation of the cell culture medium, treatment with specific drugs, and limiting certain conditions can force the cell to produce more exosomes. In this study, we have reviewed and categorized these strategies. It is hoped that the information presented in this review will provide a better understanding for expanding biotechnological approaches in exosome-based therapeutic development.

摘要

外来体是研究最多的细胞外囊泡。在许多生物学，生理学和病理学研究中，它们通过充当药物和基因的载体，已被确定为治疗和诊断疾病的合适人选。关于将外泌体用于组织再生，癌症诊断以及靶向药物/基因向特定组织的递送方面已经取得了相当大的成功。尽管外泌体的提取和纯化已取得重大进展，但提取大量外泌体仍是一项重大挑战。这个问题限制了基于外泌体的研究和治疗开发的范围。在这篇综述中，我们旨在总结专注于增加外泌体数量的实验研究。生物技术研究旨在确定外泌体生物发生的途径，以操纵某些基因以增加外泌体的产生。通常，采用两种主要策略来增加外泌体的产生。首先，对基因发生途径进行遗传操纵，以过表达外泌体生物发生的激活基因，并下调参与外泌体回收途径的基因。其次，操纵细胞培养基，用特定药物治疗以及限制某些条件会迫使细胞产生更多的外泌体。在这项研究中，我们对这些策略进行了回顾和分类。希望本综述中提供的信息将为在基于外泌体的治疗开发中扩展生物技术方法提供更好的理解。