GMP-compliant manufacturing of biologically active cell-derived vesicles produced by extrusion technology

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

doi:10.1002/jex2.70

GMP-compliant manufacturing of biologically active cell-derived vesicles produced by extrusion technology

Hui-Chong Lau, Dong Woo Han, Jinhee Park, Edwine Lehner (Co-author), Carina Anna Kals (Co-author), Claudia Arzt, Elisabeth Bayer (Co-author), Daniela Auer (Co-author), Tanja Schally (Co-author), Eva Grasmann, Han Fang (Co-author), Jae-Young Lee, Hyun Soo Lee, Jinah Han, Mario Gimona (Co-author), Eva Rohde (Co-author), Shingyu Bae, Seung Wook Oh^* (Last author)

^*Corresponding author for this work

Research output: Contribution to journal › Original Article › peer-review

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.

Translated title of the contribution	GMP-gerechte Herstellung biologisch aktiver Zellvesikel mittels Extrusionstechnologie
Original language	English
Pages (from-to)	1-18
Number of pages	18
Journal	Journal of Extracellular Biology
Volume	2022
Issue number	1:e70
DOIs	https://doi.org/10.1002/jex2.70
Publication status	Published - 25 Dec 2022

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10.1002/jex2.70

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Lau, H.-C., Han, D. W., Park, J., Lehner, E., Kals, C. A., Arzt, C., Bayer, E., Auer, D., Schally, T., Grasmann, E., Fang, H., Lee, J.-Y., Lee, H. S., Han, J., Gimona, M., Rohde, E., Bae, S., & Oh, S. W. (2022). GMP-compliant manufacturing of biologically active cell-derived vesicles produced by extrusion technology. Journal of Extracellular Biology, 2022(1:e70), 1-18. https://doi.org/10.1002/jex2.70

@article{e5cd981f9c7048d8b84b8d551fb50849,

title = "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 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{\texttrademark},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 = "EXTRUSION, GMP-konforme Herstellung, cell derived vesicles, aus Zellen gewonnene Vesikel, Medikamentenverabreichungsplattform, VESICLES, MESENCHYMAL STEM-CELLS, DRUG-DELIVERY",

author = "Hui-Chong Lau and Han, {Dong Woo} and Jinhee Park and Edwine Lehner and Kals, {Carina Anna} and Claudia Arzt and Elisabeth Bayer and Daniela Auer and Tanja Schally and Eva Grasmann and Han Fang and Jae-Young Lee and Lee, {Hyun Soo} and Jinah Han and Mario Gimona and Eva Rohde and Shingyu Bae and Oh, {Seung Wook}",

note = "Lehner, Auer, Kals, Bayer, Schally, GImona, Rohde: GMP Unit, Spinal Cord Injury & TissueRegeneration Centre Salzburg (SCI-TReCS),Paracelsus Medical University, Salzburg, Austria. Grasmann, Fang, Gimona: Transfer Centre for Extracellular VesicleTheralytic Technologies (EV-TT), Salzburg,Austria. Gimona: Research Program “Nanovesicular Therapies”,Paracelsus Medical University, Salzburg, Austria. Rohde: Department of Transfusion Medicine, UniversityHospital, Salzburger Landeskliniken GesmbH(SALK) and Paracelsus Medical University,Salzburg, Austria",

year = "2022",

month = dec,

day = "25",

doi = "10.1002/jex2.70",

language = "English",

volume = "2022",

pages = "1--18",

journal = "Journal of Extracellular Biology",

issn = "2768-2811",

publisher = "Wiley Verlag ",

number = "1:e70",

}

Lau, H-C, Han, DW, Park, J, Lehner, E, Kals, CA, Arzt, C, Bayer, E , Auer, D , Schally, T, Grasmann, E, Fang, H, Lee, J-Y, Lee, HS, Han, J, Gimona, M , Rohde, E, Bae, S & Oh, SW 2022, 'GMP-compliant manufacturing of biologically active cell-derived vesicles produced by extrusion technology', Journal of Extracellular Biology, vol. 2022, no. 1:e70, pp. 1-18. https://doi.org/10.1002/jex2.70

TY - JOUR

T1 - GMP-compliant manufacturing of biologically active cell-derived vesicles produced by extrusion technology

AU - Lau, Hui-Chong

AU - Han, Dong Woo

AU - Park, Jinhee

AU - Lehner, Edwine

AU - Kals, Carina Anna

AU - Arzt, Claudia

AU - Bayer, Elisabeth

AU - Auer, Daniela

AU - Schally, Tanja

AU - Grasmann, Eva

AU - Fang, Han

AU - Lee, Jae-Young

AU - Lee, Hyun Soo

AU - Han, Jinah

AU - Gimona, Mario

AU - Rohde, Eva

AU - Bae, Shingyu

AU - Oh, Seung Wook

N1 - Lehner, Auer, Kals, Bayer, Schally, GImona, Rohde: GMP Unit, Spinal Cord Injury & TissueRegeneration Centre Salzburg (SCI-TReCS),Paracelsus Medical University, Salzburg, Austria. Grasmann, Fang, Gimona: Transfer Centre for Extracellular VesicleTheralytic Technologies (EV-TT), Salzburg,Austria. Gimona: Research Program “Nanovesicular Therapies”,Paracelsus Medical University, Salzburg, Austria. Rohde: Department of Transfusion Medicine, UniversityHospital, Salzburger Landeskliniken GesmbH(SALK) and Paracelsus Medical University,Salzburg, Austria

PY - 2022/12/25

Y1 - 2022/12/25

N2 - 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.

AB - 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.

KW - EXTRUSION

KW - GMP-konforme Herstellung

KW - cell derived vesicles

KW - aus Zellen gewonnene Vesikel

KW - Medikamentenverabreichungsplattform

KW - VESICLES

KW - MESENCHYMAL STEM-CELLS

KW - DRUG-DELIVERY

U2 - 10.1002/jex2.70

DO - 10.1002/jex2.70

M3 - Original Article

SN - 2768-2811

VL - 2022

SP - 1

EP - 18

JO - Journal of Extracellular Biology

JF - Journal of Extracellular Biology

IS - 1:e70

ER -

GMP-compliant manufacturing of biologically active cell-derived vesicles produced by extrusion technology

Abstract

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