04 February 2019 by Laura Moreno Gutierrez

Extracellular vesicles derived from hypoxic mesenchymal stem cells prevent pulmonary vascular dysfunction induced by lipopolysaccharide.

Background:

Current evidences suggest that the therapeutic effects of mesenchymal stem cells (MSCs) are linked to their immunomodulatory and anti-inflammatory properties, mainly mediated by the secretion of extracellular vesicles (EVs). The aim of this study was to analyse whether MSCs-derived EVs are able to prevent the pulmonary vascular dysfunction induced by lipopolysaccharide (LPS).

Methods:

EVs released by umbilical cord blood-derived MSCs were obtained by differential ultracentrifugation. Rat pulmonary arteries (PA) were treated overnight with LPS in the absence or presence of EVs. IL-6 levels were determined by ELISA and nitrite accumulation by Griess assay. Contractile responses were analysed in a wire myograph in the absence or presence of DETCA (SOD inhibitor).

Results:

Exposure to LPS significantly increased IL-6 and nitrite production, inhibited hypoxic pulmonary vasoconstriction (HPV), induced endothelial dysfunction and potentiated the contractile effects induced by serotonin in isolated PA. Treatment with MSC-derived EVs had no effect in nitrite or IL-6 production but significantly prevented the impairment of HPV and the hyperresponsiveness to serotonin. In addition, EVs attenuated the endothelial dysfunction induced by either LPS or DETCA.

Conclusions:

Our data show that MSCs-derived EVs prevent the development of pulmonary vascular dysfunction induced by LPS and high oxidative stress in isolated PA. Although the mechanism remains to be determined, these results suggest that EVs could represent a new therapeutic approach in pulmonary vascular diseases associated with inflammation.

 

Supported by Spanish ISCIII (CP12/03304; PI15/01100), MECD (FPU16/05379) and Fundación contra la Hipertensión Pulmonar.

About the author


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Key Contributors

S. Esquivel-Ruiz 1, B. Barreira 1, M. Alvárez-Fuente 2, A. Gurjian1, P. Hernández-Hernández 1, Á. González-Murillo 3, M. Ramírez-Orellana 3, M. J. Del Cerro 2, Á. Cogolludo 1, F. Pérez-Vizcaíno 1, L. Moreno 1 : 1.Department of Pharmacology and Toxicology. School of Medicine, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Gregorio Marañón (IISGM) and Ciber Enfermedades Respiratorias. (CIBERES). - Madrid (Spain), 2.Hospital Universitario Ramón y Cajal - Madrid (Spain), 4.Hospital Niño Jesús, Instituto Investigación Sanitaria La Princesa - Madrid (Spain)


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