Improvement, scaling-up, and downstream analysis of exosome production

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.

Graphical Abstract

Keywords:

• Exosome production
• exosome engineering
• extracellular vesicles
• genetic engineering
• exosome biogenesis

Author contributions

Conception and design of study: Davod Jafari and Ali Samadikuchaksaraei, Acquisition of data: Davod Jafari and Sara Malih, Analysis and/or interpretation: Davod Jafari, Drafting the manuscript: Davod Jafari, Sara Malih, Maryam Eini and Rasool Jafari, Revising the manuscript critically for important intellectual content: Ali Samadikuchaksaraei, Davod Jafari, Rasool Jafari, Mazaher Gholipourmalekabadi and Majid Sadeghizadeh, Artwork preparation: Davod Jafari and Sara Malih

Disclosure statement

The authors declare that they have no conflict of interests.