Manufacturing Exosomes: A Promising Therapeutic Platform

Exosome research has been rejuvenated in recent years, due in part to the evolution in understanding of stem cell mode of action. The paracrine effect of stem cell therapy candidates has been mechanistically linked to inherited, specific functionality in secreted exosome derivatives. Even though exosomes are expected to enter clinical trials imminently, there has been a lack of manufacturing process development work that is needed to generate clinically relevant quantities of exosomes as trials progress towards larger patient numbers. If manufacturing research is not undertaken now, then the advancement of exosomes as a new therapeutic platform will be slowed. Thus, there is an urgent need for technological advancements. Here, we present process options for industrial and academic researchers to consider to translate exosomes into viable therapeutic candidates from a manufacturing perspective. Extracellular vesicles, in particular the subclass exosomes, are rapidly emerging as a novel therapeutic platform. However, currently very few clinical validation studies and no clearly defined manufacturing process exist. As exosomes progress towards the clinic for treatment of a vast array of diseases, it is important to define the engineering basis for their manufacture early in the development cycle to ensure they can be produced cost-effectively at the appropriate scale. We hypothesize that transitioning to defined manufacturing platforms will increase consistency of the exosome product and improve their clinical advancement as a new therapeutic tool. We present manufacturing technologies and strategies that are being implemented and consider their application for the transition from bench-scale to clinical production of exosomes. Extracellular vesicles, in particular the subclass exosomes, are rapidly emerging as a novel therapeutic platform. However, currently very few clinical validation studies and no clearly defined manufacturing process exist. As exosomes progress towards the clinic for treatment of a vast array of diseases, it is important to define the engineering basis for their manufacture early in the development cycle to ensure they can be produced cost-effectively at the appropriate scale. We hypothesize that transitioning to defined manufacturing platforms will increase consistency of the exosome product and improve their clinical advancement as a new therapeutic tool. We present manufacturing technologies and strategies that are being implemented and consider their application for the transition from bench-scale to clinical production of exosomes. the manufacturing steps after cell culture, which typically involve recovery, purification, washing, concentration, and formulation of the product. bioreactors that use agitation to ensure adequate mixing and mass transfer compared with static systems. an EV that is created in MVBs and then released from the cell into the extracellular environment via exocytosis. membrane-enclosed package of material that is generated via several distinct biological pathways. a modified form of cell culture flask with advanced functions, such as the separation of the liquid and air phases or compartmentalization to collect secreted products using membrane technology. a 3D bioreactor that uses parallel bundles of semipermeable capillaries that allow the transfer of nutrients and gases to the cells residing in the extracapillary spaces. a rotating blade or paddle in a bioreactor that agitates the culture medium to ensure even mixing and distribution of nutrients. the net movement of mass from one place to another. introducing oxygen bubbles into the bioreactor to dissolve oxygen in the culture medium. bioreactor technologies that use a tube filled with particles that act as a physical substrate for cell attachment and growth. They allow perfusion of the culture media to distribute nutrients and oxygen. a force experienced by cells in a bioreactor due to the flow of culture medium parallel to their surface. a method for separating and purifying biomolecules whereby the solution is passed tangentially across the filtration membrane rather than directly at it. a technique commonly used in microfluidic applications that can detect adsorption of biological material to metal surfaces.