Role of miR‐466 in mesenchymal stromal cell derived extracellular vesicles treating inoculation pneumonia caused by multidrug‐resistant Pseudomonas aeruginosa

Autor: Antoine Monsel, Jie-Ming Qu, Meng-Meng Shi, Jiayang Yan, Jean-Jacques Rouby, Ying-gang Zhu, Hanssa Dwarka Summah
Přispěvatelé: Shanghai Jiao Tong University [Shanghai], Fudan University [Shanghai], Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d’Investigation Clinique intégré en Biothérapies et immunologie [AP-HP pitié-salpêtrière, Paris] (CIC-BTi), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre d'investigation clinique Biothérapie [CHU Pitié-Salpêtrière] (CIC-BTi), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], HAL-SU, Gestionnaire
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
Stromal cell
Phagocytosis
Macrophage polarization
Medicine (miscellaneous)
[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity
Proinflammatory cytokine
Mice
03 medical and health sciences
0302 clinical medicine
Immune system
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
microRNA
Animals
Humans
pneumonia
Medicine
[SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity
Research Articles
business.industry
Mesenchymal stem cell
multidrug‐resistant pseudomonas aeruginosa
Mesenchymal Stem Cells
Drug Resistance
Multiple
In vitro
3. Good health
Mice
Inbred C57BL
Disease Models
Animal
MicroRNAs
030104 developmental biology
[SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology
[SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology
030220 oncology & carcinogenesis
Pseudomonas aeruginosa
mesenchymal stromal cell
[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Cancer research
[SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
micoRNA
Molecular Medicine
extracellular vesicles
business
Research Article
Zdroj: Clinical and Translational Medicine
Clinical and Translational Medicine, Heidelberg : Springer-Verlag, 2021, 11, pp.e287. ⟨10.1002/ctm2.287⟩
Clinical and Translational Medicine, 2021, 11, pp.e287. ⟨10.1002/ctm2.287⟩
ISSN: 2001-1326
Popis: Rationale The effects of mesenchymal stromal cells (MSCs) and MSC‐derived extracellular vesicles (MSC EVs) on multidrug‐resistant pseudomonas aeruginosa (MDR‐PA)‐induced pneumonia remain unclear. Materials and methods MicroRNA array and RT‐PCR were used to select the major microRNA in MSC EVs. Human peripheral blood monocytes were obtained and isolated from qualified patients. The crosstalk between MSCs/MSC EVs and macrophages in vitro was studied. MDR‐PA pneumonia models were further established in C57BL/6 mice and MSC EVs or miR‐466 overexpressing MSC EVs were intratracheally instilled. Results MiR‐466 was highly expressed in MSC EVs. MSCs and miR‐466 promoted macrophage polarization toward Type 2 phenotype through TIRAP‐MyD88‐NFκB axis. Moreover, cocultured macrophages with miR‐466 overexpressing MSCs significantly increased the phagocytosis of macrophages. MSC EVs significantly reduced mortality and decreased influx of BALF neutrophils, proinflammatory factor levels, protein, and bacterial load in murine MDR‐PA pneumonia. Administration of miR‐466 overexpressing MSC EVs further alleviated the inflammatory severity. Conclusions MSC‐derived EVs containing high levels of miR‐466 may partly participate in host immune responses to MDR‐PA. Both MSCs and MSC EVs have therapeutic effects in treating MDR‐PA‐induced pneumonia.
Ad‐MSC derived EVs contain high level of miR‐466. Both Ad‐MSCs and Ad‐MSC EVs have therapeutic effects in treating MDR‐PA‐induced pneumonia. miR‐466 promotes phenotype switch to M2 type of macrophages, exerting immunomodulatory effects.
Databáze: OpenAIRE
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