GMP‐compliant manufacturing of biologically active cell‐derived vesicles produced by extrusion technology
Abstract Extracellular vesicles (EVs) released by a variety of cell types have been shown to act as a natural delivery system for bioactive molecules such as RNAs and proteins. EV therapy holds great promise as a safe and cell‐free therapy for many immunological and degenerative diseases. However, t...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-12-01
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| Series: | Journal of Extracellular Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jex2.70 |
| _version_ | 1797767008016662528 |
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| author | Hui‐Chong Lau Dong Woo Han Jinhee Park Edwine Lehner Carina 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 |
| author_facet | Hui‐Chong Lau Dong Woo Han Jinhee Park Edwine Lehner Carina 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 |
| author_sort | Hui‐Chong Lau |
| collection | DOAJ |
| description | Abstract Extracellular vesicles (EVs) released by a variety of cell types have been shown to act as a natural delivery system for bioactive molecules such as RNAs and proteins. EV therapy holds great promise as a safe and cell‐free therapy for many immunological and degenerative diseases. However, translation to clinical application is limited by several factors, including insufficient large‐scale manufacturing technologies and low yield. We have developed a novel drug delivery platform technology, BioDrone™, based on cell‐derived vesicles (CDVs) produced from diverse cell sources by using a proprietary extrusion process. This extrusion technology generates nanosized vesicles in far greater numbers than naturally obtained EVs. We demonstrate that the CDVs are surrounded by a lipid bilayer membrane with a correct membrane topology. Physical, biochemical and functional characterisation results demonstrate the potential of CDVs to act as effective therapeutics. Umbilical cord mesenchymal stem cell (UCMSC)‐derived CDVs exhibit a biological activity that is similar to UCMSCs or UCMSC‐derived EVs. Lastly, we present the establishment of a GMP‐compliant process to allow the production of a large number of UCMSC‐CDVs in a reproducible manner. GMP‐compliant manufacturing of CDVs will facilitate the preclinical and clinical evaluation of these emerging therapeutics in anti‐inflammatory or regenerative medicine. This study also represents a crucial step in the development of this novel drug delivery platform based on CDVs. |
| first_indexed | 2024-03-12T20:33:30Z |
| format | Article |
| id | doaj.art-ad8f0566b4694b7780d242441d051c30 |
| institution | Directory Open Access Journal |
| issn | 2768-2811 |
| language | English |
| last_indexed | 2024-03-12T20:33:30Z |
| publishDate | 2022-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Extracellular Biology |
| spelling | doaj.art-ad8f0566b4694b7780d242441d051c302023-08-01T18:55:39ZengWileyJournal of Extracellular Biology2768-28112022-12-01112n/an/a10.1002/jex2.70GMP‐compliant manufacturing of biologically active cell‐derived vesicles produced by extrusion technologyHui‐Chong Lau0Dong Woo Han1Jinhee Park2Edwine Lehner3Carina Kals4Claudia Arzt5Elisabeth Bayer6Daniela Auer7Tanja Schally8Eva Grasmann9Han Fang10Jae‐Young Lee11Hyun Soo Lee12Jinah Han13Mario Gimona14Eva Rohde15Shingyu Bae16Seung Wook Oh17BioDrone Research Institute MDimune Inc. Seoul KoreaBioDrone Research Institute MDimune Inc. Seoul KoreaBioDrone Research Institute MDimune Inc. Seoul KoreaGMP Unit, Spinal Cord Injury & Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University Salzburg AustriaGMP Unit, Spinal Cord Injury & Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University Salzburg AustriaTransfer Centre for Extracellular Vesicle Theralytic Technologies (EV‐TT) Salzburg AustriaGMP Unit, Spinal Cord Injury & Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University Salzburg AustriaGMP Unit, Spinal Cord Injury & Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University Salzburg AustriaGMP Unit, Spinal Cord Injury & Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University Salzburg AustriaTransfer Centre for Extracellular Vesicle Theralytic Technologies (EV‐TT) Salzburg AustriaTransfer Centre for Extracellular Vesicle Theralytic Technologies (EV‐TT) Salzburg AustriaDepartment of Ophthalmology, Eunpyeong St. Mary's Hospital, College of Medicine The Catholic University of Korea Seoul KoreaDepartment of Ophthalmology, Eunpyeong St. Mary's Hospital, College of Medicine The Catholic University of Korea Seoul KoreaBioDrone Therapeutics Inc. Seattle USAGMP Unit, Spinal Cord Injury & Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University Salzburg AustriaGMP Unit, Spinal Cord Injury & Tissue Regeneration Centre Salzburg (SCI‐TReCS) Paracelsus Medical University Salzburg AustriaBioDrone Research Institute MDimune Inc. Seoul KoreaBioDrone Research Institute MDimune Inc. Seoul KoreaAbstract Extracellular vesicles (EVs) released by a variety of cell types have been shown to act as a natural delivery system for bioactive molecules such as RNAs and proteins. EV therapy holds great promise as a safe and cell‐free therapy for many immunological and degenerative diseases. However, translation to clinical application is limited by several factors, including insufficient large‐scale manufacturing technologies and low yield. We have developed a novel drug delivery platform technology, BioDrone™, based on cell‐derived vesicles (CDVs) produced from diverse cell sources by using a proprietary extrusion process. This extrusion technology generates nanosized vesicles in far greater numbers than naturally obtained EVs. We demonstrate that the CDVs are surrounded by a lipid bilayer membrane with a correct membrane topology. Physical, biochemical and functional characterisation results demonstrate the potential of CDVs to act as effective therapeutics. Umbilical cord mesenchymal stem cell (UCMSC)‐derived CDVs exhibit a biological activity that is similar to UCMSCs or UCMSC‐derived EVs. Lastly, we present the establishment of a GMP‐compliant process to allow the production of a large number of UCMSC‐CDVs in a reproducible manner. GMP‐compliant manufacturing of CDVs will facilitate the preclinical and clinical evaluation of these emerging therapeutics in anti‐inflammatory or regenerative medicine. This study also represents a crucial step in the development of this novel drug delivery platform based on CDVs.https://doi.org/10.1002/jex2.70cell‐derived vesiclesdrug delivery platformextrusionGMP‐compliant manufacturingumbilical cord mesenchymal stem cell |
| spellingShingle | Hui‐Chong Lau Dong Woo Han Jinhee Park Edwine Lehner Carina 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 GMP‐compliant manufacturing of biologically active cell‐derived vesicles produced by extrusion technology Journal of Extracellular Biology cell‐derived vesicles drug delivery platform extrusion GMP‐compliant manufacturing umbilical cord mesenchymal stem cell |
| title | GMP‐compliant manufacturing of biologically active cell‐derived vesicles produced by extrusion technology |
| title_full | GMP‐compliant manufacturing of biologically active cell‐derived vesicles produced by extrusion technology |
| title_fullStr | GMP‐compliant manufacturing of biologically active cell‐derived vesicles produced by extrusion technology |
| title_full_unstemmed | GMP‐compliant manufacturing of biologically active cell‐derived vesicles produced by extrusion technology |
| title_short | GMP‐compliant manufacturing of biologically active cell‐derived vesicles produced by extrusion technology |
| title_sort | gmp compliant manufacturing of biologically active cell derived vesicles produced by extrusion technology |
| topic | cell‐derived vesicles drug delivery platform extrusion GMP‐compliant manufacturing umbilical cord mesenchymal stem cell |
| url | https://doi.org/10.1002/jex2.70 |
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