Manufacturing Cell Vesicles for Therapy via Membrane Extrusion
Therapeutic use of extracellular vesicles seems likely to replace much of the present use of stem cell therapy, as these first generation stem cell transplantation therapies achieve benefits near entirely via the signaling generated by the transplanted cells in the short period of time in which they survive. Much of that signaling takes the form of extracellular vesicles, membrane-wrapped packages of molecules. Vesicles can be harvested from cell cultures, and are much easier to store and transport than is the case for cells, allowing centralization of the harder part of the manufacturing process that is managing stem cell cultures.
In recent years researchers have moved on from simply harvesting vesicles to finding ways to induce cells to create a lot more vesicles than is normally the case. The mechanical process of membrane extrusion is one approach to the generation of vesicles that compare favorably with naturally generated vesicles, but which are more readily produced in large amounts. In today’s open access paper, researchers combine membrane extrusion with engineered cells to produce a more favorable mix of molecules in the manufactured extracellular vesicles. The intent is to generate a therapy that can improve the environment following damage to the heart, and thereby reduce further harms and encourage greater regeneration.
Myocardial ischemia/reperfusion injury (MI/RI) remains a major challenge in the treatment of acute myocardial infarction due to the lack of effective therapeutic options. While mesenchymal stromal cells (MSCs) and their derivates show promising potential for MI/RI therapy, their clinical application is hindered by low transplantation efficiency and insufficient yield. In this study, we engineered nanoscale artificial cell-derived vesicles (ACDVs) by extruding Ginsenoside Rg1-primed MSCs (Rg1-MSCs), resulting in Rg1-ACDVs.
Rg1-ACDVs displayed superior therapeutic efficacy compared to non-primed ACDVs and extracellular vesicles derived from Rg1-MSCs (Rg1-EVs). Multi-omics analysis revealed that Rg1-ACDVs possess distinct molecular signatures associated with promoting cell cycle progression and reducing DNA damage. These findings were further validated experimentally, demonstrating that Rg1-ACDVs effectively reduce reactive oxygen species (ROS) accumulation and mitigate DNA damage both in vitro and in vivo.
This study highlights the synergistic benefits of combining Ginsenoside Rg1 priming with nanoscale engineering and introduces Rg1-ACDVs as a scalable and innovative strategy, offering a promising approach for improving clinical outcomes in MI/RI therapy.
