Quantifying extracellular vesicle heterogeneity: the effect of process conditions on protein cargo for skin therapy

Abstract Extracellular vesicles (EVs) contain a variety of proteins with anti-inflammatory and immunomodulatory properties that offer promising benefits in skin therapy applications. An influx of EV proteomic studies in recent years has created the opportunity for a detailed comparison of EV heterog...

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Main Authors: Michelle Combe, Kathy Sharon Isaac, Jordan R. Plews, Stanislav Sokolenko
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Stem Cell Research & Therapy
Subjects:
Online Access:https://doi.org/10.1186/s13287-025-04279-5
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author Michelle Combe
Kathy Sharon Isaac
Jordan R. Plews
Stanislav Sokolenko
author_facet Michelle Combe
Kathy Sharon Isaac
Jordan R. Plews
Stanislav Sokolenko
author_sort Michelle Combe
collection DOAJ
description Abstract Extracellular vesicles (EVs) contain a variety of proteins with anti-inflammatory and immunomodulatory properties that offer promising benefits in skin therapy applications. An influx of EV proteomic studies in recent years has created the opportunity for a detailed comparison of EV heterogeneity between studies in the context of therapeutic applications. Although several process conditions are known to cause variability in EVs, little has been done to quantify the impact of these factors on the nature of EV protein cargo. This review aims to both compile publicly available EV proteomics data and quantitatively estimate. the impact of process conditions on protein cargo—particularly in the context of skin therapy applications. Of roughly 400 articles, 52 relevant proteomic studies were identified within the last 15 years. Across studies, 40% of the 13,000 observed proteins were identified in only a single study. EVs in general were found to be highly variable, with mixed effects models only able to account for 25–60% of variance when considering factors such as EV source, medium, isolation method, LC-MS ionization, and protein search algorithm. Overall, MSC-derived EVs contained a greater fraction of proteins within pathways associated with wound healing and skin therapy (immune system, hemostasis, extracellular matrix organization, and cellular response to stress) as well as the most number of unique proteins when compared to all other analysed EVs. Although EVs are a promising tool within skin therapeutics, the overall variability in protein cargo underscores the need for standardized methodologies to fully elucidate the impact of process conditions on EV cargo.
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spelling doaj-art-acb2e9c386af4bcb88e1a6631e94099b2025-08-20T02:11:09ZengBMCStem Cell Research & Therapy1757-65122025-05-0116111610.1186/s13287-025-04279-5Quantifying extracellular vesicle heterogeneity: the effect of process conditions on protein cargo for skin therapyMichelle Combe0Kathy Sharon Isaac1Jordan R. Plews2Stanislav Sokolenko3Process Engineering and Applied Science, Dalhousie UniversityProcess Engineering and Applied Science, Dalhousie UniversityElevai Skincare IncProcess Engineering and Applied Science, Dalhousie UniversityAbstract Extracellular vesicles (EVs) contain a variety of proteins with anti-inflammatory and immunomodulatory properties that offer promising benefits in skin therapy applications. An influx of EV proteomic studies in recent years has created the opportunity for a detailed comparison of EV heterogeneity between studies in the context of therapeutic applications. Although several process conditions are known to cause variability in EVs, little has been done to quantify the impact of these factors on the nature of EV protein cargo. This review aims to both compile publicly available EV proteomics data and quantitatively estimate. the impact of process conditions on protein cargo—particularly in the context of skin therapy applications. Of roughly 400 articles, 52 relevant proteomic studies were identified within the last 15 years. Across studies, 40% of the 13,000 observed proteins were identified in only a single study. EVs in general were found to be highly variable, with mixed effects models only able to account for 25–60% of variance when considering factors such as EV source, medium, isolation method, LC-MS ionization, and protein search algorithm. Overall, MSC-derived EVs contained a greater fraction of proteins within pathways associated with wound healing and skin therapy (immune system, hemostasis, extracellular matrix organization, and cellular response to stress) as well as the most number of unique proteins when compared to all other analysed EVs. Although EVs are a promising tool within skin therapeutics, the overall variability in protein cargo underscores the need for standardized methodologies to fully elucidate the impact of process conditions on EV cargo.https://doi.org/10.1186/s13287-025-04279-5Extracellular vesicleProteomicsStem cell
spellingShingle Michelle Combe
Kathy Sharon Isaac
Jordan R. Plews
Stanislav Sokolenko
Quantifying extracellular vesicle heterogeneity: the effect of process conditions on protein cargo for skin therapy
Stem Cell Research & Therapy
Extracellular vesicle
Proteomics
Stem cell
title Quantifying extracellular vesicle heterogeneity: the effect of process conditions on protein cargo for skin therapy
title_full Quantifying extracellular vesicle heterogeneity: the effect of process conditions on protein cargo for skin therapy
title_fullStr Quantifying extracellular vesicle heterogeneity: the effect of process conditions on protein cargo for skin therapy
title_full_unstemmed Quantifying extracellular vesicle heterogeneity: the effect of process conditions on protein cargo for skin therapy
title_short Quantifying extracellular vesicle heterogeneity: the effect of process conditions on protein cargo for skin therapy
title_sort quantifying extracellular vesicle heterogeneity the effect of process conditions on protein cargo for skin therapy
topic Extracellular vesicle
Proteomics
Stem cell
url https://doi.org/10.1186/s13287-025-04279-5
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