Neutrophil Macrophage Crosstalk via Extracellular Vesicles Drives Reverse Migration in a Fully Human Model of Wound Healing
Abstract Persistent neutrophilic inflammation can lead to tissue damage and chronic inflammation, contributing to non‐healing wounds. The resolution phase of neutrophilic inflammation is critical to preventing tissue damage. Animal models have provided insight into resolution of neutrophilic inflamm...
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| Format: | Article |
| Language: | English |
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Wiley
2025-08-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202501036 |
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| author | Kehinde Adebayo Babatunde Oluwadamilola Fatimat Babatunde Adeel Ahmed Wilmara Salgado‐Pabon David J Beebe Sheena C. Kerr |
| author_facet | Kehinde Adebayo Babatunde Oluwadamilola Fatimat Babatunde Adeel Ahmed Wilmara Salgado‐Pabon David J Beebe Sheena C. Kerr |
| author_sort | Kehinde Adebayo Babatunde |
| collection | DOAJ |
| description | Abstract Persistent neutrophilic inflammation can lead to tissue damage and chronic inflammation, contributing to non‐healing wounds. The resolution phase of neutrophilic inflammation is critical to preventing tissue damage. Animal models have provided insight into resolution of neutrophilic inflammation via efferocytosis and reverse migration (rM); however, species‐specific differences and complexity of innate immune responses make translation to humans challenging. Thus, there is a need for in vitro systems that can elucidate mechanisms of resolution of human neutrophilic inflammation. Here, a human microphysiological system (MPS) is developed to mimic an inflammatory sterile injury (SI) microenvironment to study the role of macrophage‐derived extracellular vesicles (M‐EVs) in the resolution of inflammation via neutrophil rM. The MPS integrates a blood vessel mimic, injury site spheroid, human neutrophils, macrophages, and macrophage‐derived EVs to investigate the role of M‐EVs in neutrophil rM in vitro. The MPS enabled demonstration that EVs derived from macrophage subsets modulate migratory behavior in primary neutrophils differently in specific inflammatory microenvironments. A new mechanism is identified underlying neutrophil rM, where neutrophils exposed to M2‐EV‐derived‐IL‐8 migrate away from the SI site. Overall, the SI MPS system demonstrates a reverse migratory pattern in human primary neutrophils, advancing the study of the resolution of inflammation via M‐EVs. |
| format | Article |
| id | doaj-art-9eb281a503ce41d48557e9b6b4b754ec |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-9eb281a503ce41d48557e9b6b4b754ec2025-08-23T14:14:45ZengWileyAdvanced Science2198-38442025-08-011231n/an/a10.1002/advs.202501036Neutrophil Macrophage Crosstalk via Extracellular Vesicles Drives Reverse Migration in a Fully Human Model of Wound HealingKehinde Adebayo Babatunde0Oluwadamilola Fatimat Babatunde1Adeel Ahmed2Wilmara Salgado‐Pabon3David J Beebe4Sheena C. Kerr5Department of Pathology & Laboratory Medicine University of Wisconsin Madison WI 53705 USADepartment of Veterinary Medicine University of Wisconsin Madison WI 53706 USADepartment of Pathology & Laboratory Medicine University of Wisconsin Madison WI 53705 USADepartment of Veterinary Medicine University of Wisconsin Madison WI 53706 USADepartment of Pathology & Laboratory Medicine University of Wisconsin Madison WI 53705 USACarbone Cancer Center University of Wisconsin Madison WI 53792 USAAbstract Persistent neutrophilic inflammation can lead to tissue damage and chronic inflammation, contributing to non‐healing wounds. The resolution phase of neutrophilic inflammation is critical to preventing tissue damage. Animal models have provided insight into resolution of neutrophilic inflammation via efferocytosis and reverse migration (rM); however, species‐specific differences and complexity of innate immune responses make translation to humans challenging. Thus, there is a need for in vitro systems that can elucidate mechanisms of resolution of human neutrophilic inflammation. Here, a human microphysiological system (MPS) is developed to mimic an inflammatory sterile injury (SI) microenvironment to study the role of macrophage‐derived extracellular vesicles (M‐EVs) in the resolution of inflammation via neutrophil rM. The MPS integrates a blood vessel mimic, injury site spheroid, human neutrophils, macrophages, and macrophage‐derived EVs to investigate the role of M‐EVs in neutrophil rM in vitro. The MPS enabled demonstration that EVs derived from macrophage subsets modulate migratory behavior in primary neutrophils differently in specific inflammatory microenvironments. A new mechanism is identified underlying neutrophil rM, where neutrophils exposed to M2‐EV‐derived‐IL‐8 migrate away from the SI site. Overall, the SI MPS system demonstrates a reverse migratory pattern in human primary neutrophils, advancing the study of the resolution of inflammation via M‐EVs.https://doi.org/10.1002/advs.202501036extracellular vesiclesmicrophysiological systemneutrophilsreverse migration |
| spellingShingle | Kehinde Adebayo Babatunde Oluwadamilola Fatimat Babatunde Adeel Ahmed Wilmara Salgado‐Pabon David J Beebe Sheena C. Kerr Neutrophil Macrophage Crosstalk via Extracellular Vesicles Drives Reverse Migration in a Fully Human Model of Wound Healing Advanced Science extracellular vesicles microphysiological system neutrophils reverse migration |
| title | Neutrophil Macrophage Crosstalk via Extracellular Vesicles Drives Reverse Migration in a Fully Human Model of Wound Healing |
| title_full | Neutrophil Macrophage Crosstalk via Extracellular Vesicles Drives Reverse Migration in a Fully Human Model of Wound Healing |
| title_fullStr | Neutrophil Macrophage Crosstalk via Extracellular Vesicles Drives Reverse Migration in a Fully Human Model of Wound Healing |
| title_full_unstemmed | Neutrophil Macrophage Crosstalk via Extracellular Vesicles Drives Reverse Migration in a Fully Human Model of Wound Healing |
| title_short | Neutrophil Macrophage Crosstalk via Extracellular Vesicles Drives Reverse Migration in a Fully Human Model of Wound Healing |
| title_sort | neutrophil macrophage crosstalk via extracellular vesicles drives reverse migration in a fully human model of wound healing |
| topic | extracellular vesicles microphysiological system neutrophils reverse migration |
| url | https://doi.org/10.1002/advs.202501036 |
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