Royal jelly extracellular vesicles promote wound healing by modulating underlying cellular responses

Apis mellifera royal jelly (RJ) is a well-known remedy in traditional medicine around the world and its versatile effects range from antibacterial to anti-inflammatory properties and pro-regenerative properties. As a glandular product, RJ has been shown to contain a substantial number of extracellul...

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Main Authors: Simón Álvarez, Pamina Contreras-Kallens, Sebastian Aguayo, Orlando Ramírez, Catalina Vallejos, Jorge Ruiz, Eva Carrasco-Gallardo, Stefanie Troncoso-Vera, Bernardo Morales, Christina M.A.P. Schuh
Format: Article
Language:English
Published: Elsevier 2023-03-01
Series:Molecular Therapy: Nucleic Acids
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2162253123000288
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author Simón Álvarez
Pamina Contreras-Kallens
Sebastian Aguayo
Orlando Ramírez
Catalina Vallejos
Jorge Ruiz
Eva Carrasco-Gallardo
Stefanie Troncoso-Vera
Bernardo Morales
Christina M.A.P. Schuh
author_facet Simón Álvarez
Pamina Contreras-Kallens
Sebastian Aguayo
Orlando Ramírez
Catalina Vallejos
Jorge Ruiz
Eva Carrasco-Gallardo
Stefanie Troncoso-Vera
Bernardo Morales
Christina M.A.P. Schuh
author_sort Simón Álvarez
collection DOAJ
description Apis mellifera royal jelly (RJ) is a well-known remedy in traditional medicine around the world and its versatile effects range from antibacterial to anti-inflammatory properties and pro-regenerative properties. As a glandular product, RJ has been shown to contain a substantial number of extracellular vesicles (EVs), and, in this study, we aimed to investigate the extent of involvement of RJEVs in wound healing-associated effects. Molecular analysis of RJEVs verified the presence of exosomal markers such as CD63 and syntenin, and cargo molecules MRJP1, defensin-1, and jellein-3. Furthermore, RJEVs were demonstrated to modulate mesenchymal stem cell (MSC) differentiation and secretome, as well as decrease LPS-induced inflammation in macrophages by blocking the mitogen-activated protein kinase (MAPK) pathway. In vivo studies confirmed antibacterial effects of RJEVs and demonstrated an acceleration of wound healing in a splinted mouse model. This study suggests that RJEVs play a crucial role in the known effects of RJ by modulating the inflammatory phase and cellular response in wound healing. Transfer of RJ into the clinics has been impeded by the high complexity of the raw material. Isolating EVs from the raw RJ decreases the complexity while allowing standardization and quality control, bringing a natural nano-therapy one step closer to the clinics.
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spelling doaj.art-798dd39777be48edb0b648efdb2796d12023-02-28T04:08:38ZengElsevierMolecular Therapy: Nucleic Acids2162-25312023-03-0131541552Royal jelly extracellular vesicles promote wound healing by modulating underlying cellular responsesSimón Álvarez0Pamina Contreras-Kallens1Sebastian Aguayo2Orlando Ramírez3Catalina Vallejos4Jorge Ruiz5Eva Carrasco-Gallardo6Stefanie Troncoso-Vera7Bernardo Morales8Christina M.A.P. Schuh9Centro de Medicina Regenerativa, Facultad de Medicina, Clínica Alemana-Universidad del Desarrollo, Santiago, ChileCentro de Medicina Regenerativa, Facultad de Medicina, Clínica Alemana-Universidad del Desarrollo, Santiago, ChileDentistry School, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; Institute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, ChileCentro de Medicina Regenerativa, Facultad de Medicina, Clínica Alemana-Universidad del Desarrollo, Santiago, ChileLaboratorio de Medicina Experimental, Facultad de Medicina, Clínica Alemana-Universidad del Desarrollo, Santiago, ChileLaboratorio de Medicina Experimental, Facultad de Medicina, Clínica Alemana-Universidad del Desarrollo, Santiago, ChileLaboratorio de Histopatología, Cemesi, Santiago, ChileLaboratorio de Histopatología, Cemesi, Santiago, ChileFacultad de Salud, Universidad del Alba, Santiago, ChileCentro de Medicina Regenerativa, Facultad de Medicina, Clínica Alemana-Universidad del Desarrollo, Santiago, Chile; Corresponding author. Christina Schuh, Clínica Alemana-Universidad del Desarrollo, Avenida Plaza 680, Las Condes, Santiago de Chile.Apis mellifera royal jelly (RJ) is a well-known remedy in traditional medicine around the world and its versatile effects range from antibacterial to anti-inflammatory properties and pro-regenerative properties. As a glandular product, RJ has been shown to contain a substantial number of extracellular vesicles (EVs), and, in this study, we aimed to investigate the extent of involvement of RJEVs in wound healing-associated effects. Molecular analysis of RJEVs verified the presence of exosomal markers such as CD63 and syntenin, and cargo molecules MRJP1, defensin-1, and jellein-3. Furthermore, RJEVs were demonstrated to modulate mesenchymal stem cell (MSC) differentiation and secretome, as well as decrease LPS-induced inflammation in macrophages by blocking the mitogen-activated protein kinase (MAPK) pathway. In vivo studies confirmed antibacterial effects of RJEVs and demonstrated an acceleration of wound healing in a splinted mouse model. This study suggests that RJEVs play a crucial role in the known effects of RJ by modulating the inflammatory phase and cellular response in wound healing. Transfer of RJ into the clinics has been impeded by the high complexity of the raw material. Isolating EVs from the raw RJ decreases the complexity while allowing standardization and quality control, bringing a natural nano-therapy one step closer to the clinics.http://www.sciencedirect.com/science/article/pii/S2162253123000288MT: Special Issue - Exploiting Extracellular Vesicles as Therapeutic Agentsinterkingdom communicationanti-inflammatory extracellular vesiclesnano-therapydefensin-1extracellular vesicle delivery
spellingShingle Simón Álvarez
Pamina Contreras-Kallens
Sebastian Aguayo
Orlando Ramírez
Catalina Vallejos
Jorge Ruiz
Eva Carrasco-Gallardo
Stefanie Troncoso-Vera
Bernardo Morales
Christina M.A.P. Schuh
Royal jelly extracellular vesicles promote wound healing by modulating underlying cellular responses
Molecular Therapy: Nucleic Acids
MT: Special Issue - Exploiting Extracellular Vesicles as Therapeutic Agents
interkingdom communication
anti-inflammatory extracellular vesicles
nano-therapy
defensin-1
extracellular vesicle delivery
title Royal jelly extracellular vesicles promote wound healing by modulating underlying cellular responses
title_full Royal jelly extracellular vesicles promote wound healing by modulating underlying cellular responses
title_fullStr Royal jelly extracellular vesicles promote wound healing by modulating underlying cellular responses
title_full_unstemmed Royal jelly extracellular vesicles promote wound healing by modulating underlying cellular responses
title_short Royal jelly extracellular vesicles promote wound healing by modulating underlying cellular responses
title_sort royal jelly extracellular vesicles promote wound healing by modulating underlying cellular responses
topic MT: Special Issue - Exploiting Extracellular Vesicles as Therapeutic Agents
interkingdom communication
anti-inflammatory extracellular vesicles
nano-therapy
defensin-1
extracellular vesicle delivery
url http://www.sciencedirect.com/science/article/pii/S2162253123000288
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