Research & Innovation
Publications
GMP-compliant manufacturing of biologically active cell-derived vesicles produced by extrusion technology
PMU Authors
Edwine Lehner, Carina Anna Kals, Claudia Arzt, Elisabeth Bayer, Daniela Auer, Tanja Schally, Eva Grasmann, Han Fang, Mario Gimona, Eva Rohde
All Authors
Hui-Chong Lau, Dong Woo Han, Jinhee Park, Edwine Lehner, Carina Anna Kals, Claudia Arzt, Elisabeth Bayer, Daniela Auer, Tanja Schally, Eva Grasmann, Han Fang, Jae-Young Lee, Hyun Soo Lee, Jinah Han, Mario Gimona, Eva Rohde, Shingyu Bae, Seung Wook Oh
Journal association
Journal of Extracellular Biology
Abstract
Extracellular vesicles (EVs) released by a variety of cell types have been shown to actas a natural delivery system for bioactive molecules such as RNAs and proteins. EVtherapy holds great promise as a safe and cell-free therapy for many immunologi-cal and degenerative diseases. However, translation to clinical application is limitedby several factors, including insufficient large-scale manufacturing technologies andlow yield. We have developed a novel drug delivery platform technology, BioDrone™,based on cell-derived vesicles (CDVs) produced from diverse cell sources by using aproprietary extrusion process. This extrusion technology generates nanosized vesi-cles in far greater numbers than naturally obtained EVs. We demonstrate that theCDVs are surrounded by a lipid bilayer membrane with a correct membrane topology.Physical, biochemical and functional characterisation results demonstrate the poten-tial of CDVs to act as effective therapeutics. Umbilical cord mesenchymal stem cell(UCMSC)-derived CDVs exhibit a biological activity that is similar to UCMSCs orUCMSC-derived EVs. Lastly, we present the establishment of a GMP-compliant pro-cess to allow the production of a large number of UCMSC-CDVs in a reproduciblemanner. GMP-compliant manufacturing of CDVs will facilitate the preclinical andclinical evaluation of these emerging therapeutics in anti-inflammatory or regener-ative medicine. This study also represents a crucial step in the development of thisnovel drug delivery platform based on CDVs.
Keywords
MESENCHYMAL STEM-CELLS, EXTRUSION, VESICLES, DRUG-DELIVERY, GMP-konforme Herstellung, cell derived vesicles, aus Zellen gewonnene Vesikel, Medikamentenverabreichungsplattform