Bone mesenchymal stromal cell-derived small extracellular vesicles inhibit inflammation and ameliorate sepsis via delivery of microRNA-21a-5p |
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| Affiliation: | 1. Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, China;2. Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China;3. Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, China;4. Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, China;5. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China;6. Department of Respiratory Medicine, Second Affiliated Hospital of Xinjiang Medical University, Urumqi, China;7. Department of Hepatobiliary Surgery, Chinese People''s Liberation Army General Hospital, Chinese People''s Liberation Army Medical College, Beijing, China;8. Institute of Hepatobiliary Surgery, Chinese People''s Liberation Army General Hospital, Chinese People''s Liberation Army Medical College, Beijing, China;9. Department of Pathology, Xiangya Hospital, Central South University, Changsha, China;10. Department of Infectious Disease, People''s Hospital of Liuyang City, Liuyang, China;11. Institute of Basic Medicine Science, Chinese People''s Liberation Army General Hospital, Chinese People''s Liberation Army Medical College, Beijing, China;12. Center of Pulmonary and Critical Care Medicine, Chinese People''s Liberation Army General Hospital, Chinese People''s Liberation Army Medical College, Beijing, China |
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| Abstract: | Background aimsSepsis is a potentially life-threatening disease that results from a severe systemic inflammatory response due to infection. Mesenchymal stromal cell-derived small extracellular vesicles (MSC sEVs) are able to transfer bioactive molecules and have been demonstrated to play an important role in the pathophysiological process of sepsis. Herein the authors aimed to investigate the potential role and downstream molecular mechanism of MSC sEVs in sepsis.MethodsMSC sEVs were acquired by ultracentrifugation and then injected into a cecal ligation and puncture mouse model. The efficacy of MSC sEVs in both in vitro and in vivo models of sepsis was evaluated.ResultsMSC sEV therapy improved survival, reduced sepsis-induced inflammation, attenuated pulmonary capillary permeability and improved liver and kidney function in septic mice. In addition, the authors found that microRNA-21a-5p (miR-21a-5p) was highly enriched in MSC sEVs, could be transferred to recipient cells, inhibited inflammation and increased survival in septic mice. Furthermore, the authors demonstrated that MSC sEV miR-21a-5p suppressed inflammation by targeting toll-like receptor 4 and programmed cell death 4. The therapeutic efficacy of MSC sEVs was partially abrogated by transfection with miR-21a-5p inhibitors.ConclusionsCollectively, the authors’ data suggest that miR-21a-5p-bearing MSC sEVs may be a prospective and effective sepsis therapeutic strategy. |
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