Bovine milk exosomes affected proliferation of macrophages under hypoxia

Matic, Svjetlana; Dia, Vermont P.

doi:10.1016/j.crfs.2022.11.002

Cited by 9 publications

(8 citation statements)

References 37 publications

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“…In general, hypoxic conditions affect ROS levels [13,14], suggesting that the ROS level is increased under hypoxia. Contrary, reports from other studies [15,16] showed that hypoxia caused a ROS level decrease compared to normoxic conditions in a pre-osteoblastic cell line and in macrophages. Thus, our first aim was to determine how hypoxia would affect the osteogenic differentiation ability of naïve hBMSCs and if it increases ROS production.…”

Section: Introductioncontrasting

confidence: 81%

Extracellular Vesicles Derived from Osteogenic-Differentiated Human Bone Marrow-Derived Mesenchymal Cells Rescue Osteogenic Ability of Bone Marrow-Derived Mesenchymal Cells Impaired by Hypoxia

Wang,

Stöckl,

Pattappa

et al. 2023

Biomedicines

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In orthopedics, musculoskeletal disorders, i.e., non-union of bone fractures or osteoporosis, can have common histories and symptoms related to pathological hypoxic conditions induced by aging, trauma or metabolic disorders. Here, we observed that hypoxic conditions (2% O2) suppressed the osteogenic differentiation of human bone marrow-derived mesenchymal cells (hBMSC) in vitro and simultaneously increased reactive oxygen species (ROS) production. We assumed that cellular origin and cargo of extracellular vesicles (EVs) affect the osteogenic differentiation capacity of hBMSCs cultured under different oxygen pressures. Proteomic analysis revealed that EVs isolated from osteogenic differentiated hBMSC cultured under hypoxia (hypo-osteo EVs) or under normoxia (norm-osteo EVs) contained distinct protein profiles. Extracellular matrix (ECM) components, antioxidants and pro-osteogenic proteins were decreased in hypo-osteo EVs. The proteomic analysis in our previous study revealed that under normoxic culture conditions, pro-osteogenic proteins and ECM components have higher concentrations in norm-osteo EVs than in EVs derived from naïve hBMSCs (norm-naïve EVs). When selected for further analysis, five anti-hypoxic proteins were significantly upregulated (response to hypoxia) in norm-osteo EVs. Three of them are characterized as antioxidant proteins. We performed qRT-PCR to verify the corresponding gene expression levels in the norm-osteo EVs’ and norm-naïve EVs’ parent cells cultured under normoxia. Moreover, we observed that norm-osteo EVs rescued the osteogenic ability of naïve hBMSCs cultured under hypoxia and reduced hypoxia-induced elevation of ROS production in osteogenic differentiated hBMSCs, presumably by inducing expression of anti-hypoxic/ antioxidant and pro-osteogenic genes.

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Section: Introductioncontrasting

confidence: 81%

Extracellular Vesicles Derived from Osteogenic-Differentiated Human Bone Marrow-Derived Mesenchymal Cells Rescue Osteogenic Ability of Bone Marrow-Derived Mesenchymal Cells Impaired by Hypoxia

Wang,

Stöckl,

Pattappa

et al. 2023

Biomedicines

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“…The size of mEVs (<150 nm) falls within the range of those reported previously [ 24 ] and, likewise, zeta‐potential (−9.1 ± 0.65 mV) is similar to previous reports for mEVs. [ 25 ] The expression of mEV protein markers was identified using Exo‐Check Array, as shown in Figure S1 (Supporting Information). mEVs expressed general markers including CD63, CD81, ICAM (Intercellular Adhesion Molecule‐1) and TSG101 (Tumor Susceptibility Gene 101), while ALIX (ALG‐2‐interacting protein X) is not apparent (this protein exists in EVs from colostrum and not mature milk).…”

Section: Resultsmentioning

confidence: 99%

“…This could have resulted from a cell proliferation inducing property of mEVs, which has been confirmed in previous reports for intestinal cells and macrophages. [ 25,28 ]…”

Section: Resultsmentioning

confidence: 99%

Hybrid Milk Extracellular Vesicles as Potential Systems for Oral Delivery of siRNA

Zhang,

Luo,

Ding

et al. 2024

Advanced Therapeutics

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Oral administration of RNA is currently not possible and current approaches for RNA delivery by injection are not suitable for the oral route. In this work, we report novel bioinspired nanoparticles for oral delivery of RNA therapies. Specifically, we report the fabrication of hybrid nanovesicles (“hybridosomes”) based on bovine milk extracellular vesicles (mEVs) and liposomes. Hybridosomes were fabricated using two related methods based on freeze‐thawing of mEVs and cationic liposomes. The systems were 180–230 nm and demonstrated efficient loading of siRNA cargo. Hybridosomes exhibited significantly lower cytotoxicity in intestinal Caco‐2 cells compared to cationic liposomes and superior stability in a fed‐state simulated intestinal fluid compared to liposomes. Furthermore, these systems significantly increased the transport of siRNA across in vitro intestinal model. Finally, hybridosomes loaded with siRNA successfully induced transfection in J774A.1 macrophages. Overall, our results show that the hybrid systems fabricated here offer potential for oral delivery of RNA therapeutics.This article is protected by copyright. All rights reserved

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“…However, recent works have instead pointed towards an antioxidant and protective role of exosomes against oxidative stress 43 . For example, bovine MEx inhibit ROS production, increase activities of the antioxidant enzymes SOD and GPX 44 , and suppress murine macrophages ROS production under hypoxic conditions 45 .…”

Section: Discussionmentioning

confidence: 99%

Porcine milk exosomes modulate the immune functions of CD14+ monocytes in vitro

Morales,

De Leonardis,

Filipe

et al. 2023

Preprint

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Exosomes mediate near and long-distance intercellular communication by transferring their molecular cargo to recipient cells, altering their biological response. Milk exosomes (MEx) are internalized by immune cells and exert immunomodulatory functions in vitro. Porcine MEx can accumulate in the small intestine, rich in macrophages. No information is available on the immunomodulatory ability of porcine MEx on porcine monocytes, which are known precursors of gut macrophages. Therefore, this study aims at (1) assessing the in vitro uptake of porcine MEx by porcine monocytes (CD14+), and (2) evaluating the in vitro impact of porcine MEx on porcine monocytes immune functions. MEx were purified by ultracentrifugation and size exclusion chromatography (SEC). The monocytes’ internalization of PKH26-labeled MEx was examined using fluorescence microscopy. Monocytes were incubated with increasing exosome concentrations and their apoptosis and viability were measured. Lastly, the ability of MEx to modulate the cells’ immune activities was evaluated by measuring monocytes’ phagocytosis, the capacity of killing bacteria, chemotaxis, and reactive oxygen species (ROS) production. MEx were internalized by porcine monocytes in vitro. They also decreased their chemotaxis and phagocytosis, and increased ROS production. Altogether, this study provides insights into the role that MEx might play in pigs’ immunity by demonstrating that MEx are internalized by porcine monocytes in vitro and exert immunomodulatory effects on inflammatory functions.

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Bovine milk exosomes affected proliferation of macrophages under hypoxia

Cited by 9 publications

References 37 publications

Extracellular Vesicles Derived from Osteogenic-Differentiated Human Bone Marrow-Derived Mesenchymal Cells Rescue Osteogenic Ability of Bone Marrow-Derived Mesenchymal Cells Impaired by Hypoxia

Extracellular Vesicles Derived from Osteogenic-Differentiated Human Bone Marrow-Derived Mesenchymal Cells Rescue Osteogenic Ability of Bone Marrow-Derived Mesenchymal Cells Impaired by Hypoxia

Hybrid Milk Extracellular Vesicles as Potential Systems for Oral Delivery of siRNA

Porcine milk exosomes modulate the immune functions of CD14+ monocytes in vitro

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