Current Strategies for Promoting the Large-scale Production of Exosomes

Abstract

Exosomes, as nanoscale biological vesicles, have been shown to have great potential for biomedical applications. However, the low yield of exosomes limits their application. In this review, we focus on methods to increase exosome yield. Two main strategies are used to increase exosome production, one is based on genetic manipulation of the exosome biogenesis and release pathway, and the other is by pretreating parent cells, changing the culture method or adding different components to the medium. By applying these strategies, exosomes can be produced on a large scale to facilitate their practical application in the clinic.

The remodeling of ovarian function: targeted delivery strategies for mesenchymal stem cells and their derived extracellular vesicles

“…Conventional methods to enhance EVs secretion are difficult to meet the needs of large-scale EVs production, such as (1) genetic engineering based on exosome biogenesis and release pathways, (2) pretreatment of parental cells or addition of different additives to the culture medium, and (3) 3D cell culture based on biomaterials [ 110 ]. For large-scale production, the current mainstream means is to 3D culture large quantities of MSCs in rotating flasks based on microcarriers.…”

Non-stem cell-derived exosomes: a novel therapeutics for neurotrauma

“…Recent developments in clinical-grade exosome production have been reported, including the work of Mayela Mendt et al, who described a bioreactor-based, large-scale production of clinical-grade exosomes adhering to Good Manufacturing Practice (GMP) standards [ 123 ]. Although there are various methods to augment the production of exosomes, such as engineering modifications to exosomes and stimulation with exogenous drugs, enhancing exosome yield at the source remains a principal strategy [ 124 ]. Secondly, the selection of isolation approaches to facilitate exosome production also presents challenges, with each method having its advantages and drawbacks.…”

Insight into the Functional Dynamics and Challenges of Exosomes in Pharmaceutical Innovation and Precision Medicine

“…In a controlled laboratory setting, extraction from one milliliter of cell culture medium frequently results in less than one microgram of exosomal protein [ 29 ]. Strategies to augment exosome production have been explored, encompassing mechanical (e.g., three-dimensional culture systems and the application of shear stress), biochemical (e.g., treatment with lipopolysaccharide (LPS), interferon-gamma (IFN-γ), bone morphogenetic protein 2 (BMP-2), tumor necrosis factor-alpha (TNF-α), and hypoxia-inducible factor 1-alpha (HIF-1α)), and physical (e.g., thermal stress, hypoxic conditions, and nutrient deprivation) methodologies [ 30 , 31 , 32 ].…”