Industrial Scale Production and Characterization of a Whey Fraction Enriched in Extracellular Vesicle Material

ABSTRACT Human milk serves the sole nutritional role for the developing infant. During lactation, nano‐sized extracellular vesicles (EVs) in milk containing a multitude of biologically active components are transferred from mother to offspring. Infant formula (IF) based on cow milk‐derived ingredien...

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Main Authors: Søren Roi Midtgaard, Maria Stenum Hansen, Nikolaj Drachmann, Xiaolu Geng, Kristine Ingrid Marie Blans, Manja Mahmens Fabricius Møbjerg, Anny F. Frølund, Jan Trige Rasmussen, Marie Stampe Ostenfeld
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Journal of Extracellular Biology
Online Access:https://doi.org/10.1002/jex2.70044
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author Søren Roi Midtgaard
Maria Stenum Hansen
Nikolaj Drachmann
Xiaolu Geng
Kristine Ingrid Marie Blans
Manja Mahmens Fabricius Møbjerg
Anny F. Frølund
Jan Trige Rasmussen
Marie Stampe Ostenfeld
author_facet Søren Roi Midtgaard
Maria Stenum Hansen
Nikolaj Drachmann
Xiaolu Geng
Kristine Ingrid Marie Blans
Manja Mahmens Fabricius Møbjerg
Anny F. Frølund
Jan Trige Rasmussen
Marie Stampe Ostenfeld
author_sort Søren Roi Midtgaard
collection DOAJ
description ABSTRACT Human milk serves the sole nutritional role for the developing infant. During lactation, nano‐sized extracellular vesicles (EVs) in milk containing a multitude of biologically active components are transferred from mother to offspring. Infant formula (IF) based on cow milk‐derived ingredients has been reported to contain reduced levels of EVs as compared to human milk. There is therefore an unmet need to produce large‐scale volumes of milk EVs to improve IF composition. Here, we report a scalable industrial production protocol for a bovine whey‐derived ingredient that is highly enriched in EV material using a large‐scale sequential ceramic membrane filtration setup. Furthermore, we demonstrate a robust and generally applicable analytical approach to determine the relative contributions of EVs and milk fat globule membrane (MFGM) using molar ratios of the membrane‐bound proteins butyrophilin (BTN) and CD9 as surrogate markers for MFGM and EVs, respectively. Taken together, our findings provide a basis for comparing bovine milk‐containing foods and aid in developing specialized ingredients that can minimize the compositional difference between infant formula and human milk.
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publishDate 2025-05-01
publisher Wiley
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series Journal of Extracellular Biology
spelling doaj-art-574375fe0ce54c2ba9a8f2b5d350282b2025-08-20T01:56:49ZengWileyJournal of Extracellular Biology2768-28112025-05-0145n/an/a10.1002/jex2.70044Industrial Scale Production and Characterization of a Whey Fraction Enriched in Extracellular Vesicle MaterialSøren Roi Midtgaard0Maria Stenum Hansen1Nikolaj Drachmann2Xiaolu Geng3Kristine Ingrid Marie Blans4Manja Mahmens Fabricius Møbjerg5Anny F. Frølund6Jan Trige Rasmussen7Marie Stampe Ostenfeld8Arla Foods Ingredients Group PS Viby Central Jutland Region DenmarkArla Foods Ingredients Group PS Viby Central Jutland Region DenmarkArla Foods Ingredients Group PS Viby Central Jutland Region DenmarkArla Foods Ingredients Group PS Viby Central Jutland Region DenmarkArla Foods Ingredients Group PS Viby Central Jutland Region DenmarkArla Foods Ingredients Group PS Viby Central Jutland Region DenmarkArla Foods Ingredients Group PS Viby Central Jutland Region DenmarkAarhus Universitet Aarhus Central Jutland Region DenmarkArla Foods Ingredients Group PS Viby Central Jutland Region DenmarkABSTRACT Human milk serves the sole nutritional role for the developing infant. During lactation, nano‐sized extracellular vesicles (EVs) in milk containing a multitude of biologically active components are transferred from mother to offspring. Infant formula (IF) based on cow milk‐derived ingredients has been reported to contain reduced levels of EVs as compared to human milk. There is therefore an unmet need to produce large‐scale volumes of milk EVs to improve IF composition. Here, we report a scalable industrial production protocol for a bovine whey‐derived ingredient that is highly enriched in EV material using a large‐scale sequential ceramic membrane filtration setup. Furthermore, we demonstrate a robust and generally applicable analytical approach to determine the relative contributions of EVs and milk fat globule membrane (MFGM) using molar ratios of the membrane‐bound proteins butyrophilin (BTN) and CD9 as surrogate markers for MFGM and EVs, respectively. Taken together, our findings provide a basis for comparing bovine milk‐containing foods and aid in developing specialized ingredients that can minimize the compositional difference between infant formula and human milk.https://doi.org/10.1002/jex2.70044
spellingShingle Søren Roi Midtgaard
Maria Stenum Hansen
Nikolaj Drachmann
Xiaolu Geng
Kristine Ingrid Marie Blans
Manja Mahmens Fabricius Møbjerg
Anny F. Frølund
Jan Trige Rasmussen
Marie Stampe Ostenfeld
Industrial Scale Production and Characterization of a Whey Fraction Enriched in Extracellular Vesicle Material
Journal of Extracellular Biology
title Industrial Scale Production and Characterization of a Whey Fraction Enriched in Extracellular Vesicle Material
title_full Industrial Scale Production and Characterization of a Whey Fraction Enriched in Extracellular Vesicle Material
title_fullStr Industrial Scale Production and Characterization of a Whey Fraction Enriched in Extracellular Vesicle Material
title_full_unstemmed Industrial Scale Production and Characterization of a Whey Fraction Enriched in Extracellular Vesicle Material
title_short Industrial Scale Production and Characterization of a Whey Fraction Enriched in Extracellular Vesicle Material
title_sort industrial scale production and characterization of a whey fraction enriched in extracellular vesicle material
url https://doi.org/10.1002/jex2.70044
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