Effect of human mesenchymal stem cell secretome administration on morphine self-administration and relapse in two animal models of opioid dependence

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dc.contributor.authorQuintanilla, María Elena
dc.contributor.authorQuezada, Mauricio
dc.contributor.authorMorales, Paola
dc.contributor.authorBerríos, Pablo
dc.contributor.authorSantapau, Daniela
dc.contributor.authorEzquer, Marcelo
dc.contributor.authorHerrera, Mario
dc.contributor.authorIsrael, Yedy
dc.contributor.authorEzquer, Fernando
dc.date.accessioned2022-11-14T16:34:50Z
dc.date.available2022-11-14T16:34:50Z
dc.date.issued2022
dc.description.abstractThe present study investigates the possible therapeutic effects of human mesenchymal stem cell-derived secretome on morphine dependence and relapse. This was studied in a new model of chronic voluntary morphine intake in Wistar rats which shows classic signs of morphine intoxication and a severe naloxone-induced withdrawal syndrome. A single intranasal-systemic administration of MSCs secretome fully inhibited (>95%; p < 0.001) voluntary morphine intake and reduced the post-deprivation relapse intake by 50% (p < 0.02). Since several studies suggest a significant genetic contribution to the chronic use of many addictive drugs, the effect of MSCs secretome on morphine self-administration was further studied in rats bred as high alcohol consumers (UChB rats). Sub-chronic intraperitoneal administration of morphine before access to increasing concentrations of morphine solutions and water were available to the animals, led UChB rats to prefer ingesting morphine solutions over water, attaining levels of oral morphine intake in the range of those in the Wistar model. Intranasally administered MSCs secretome to UChB rats dose-dependently inhibited morphine self-administration by 72% (p < 0.001); while a single intranasal dose of MSC-secretome administered during a morphine deprivation period imposed on chronic morphine consumer UChB rats inhibited re-access morphine relapse intake by 80 to 85% (p < 0.0001). Both in the Wistar and the UChB rat models, MSCs-secretome administration reversed the morphine-induced increases in brain oxidative stress and neuroinflammation, considered as key engines perpetuating drug relapse. Overall, present preclinical studies suggest that products secreted by human mesenchymal stem cells may be of value in the treatment of opioid addiction.es
dc.description.versionVersión publicadaes
dc.identifier.citationThe present study investigates the possible therapeutic effects of human mesenchymal stem cell-derived secretome on morphine dependence and relapse. This was studied in a new model of chronic voluntary morphine intake in Wistar rats which shows classic signs of morphine intoxication and a severe naloxone-induced withdrawal syndrome. A single intranasal-systemic administration of MSCs secretome fully inhibited (>95%; p < 0.001) voluntary morphine intake and reduced the post-deprivation relapse intake by 50% (p < 0.02). Since several studies suggest a significant genetic contribution to the chronic use of many addictive drugs, the effect of MSCs secretome on morphine self-administration was further studied in rats bred as high alcohol consumers (UChB rats). Sub-chronic intraperitoneal administration of morphine before access to increasing concentrations of morphine solutions and water were available to the animals, led UChB rats to prefer ingesting morphine solutions over water, attaining levels of oral morphine intake in the range of those in the Wistar model. Intranasally administered MSCs secretome to UChB rats dosedependently inhibited morphine self-administration by 72% (p < 0.001); while a single intranasal dose of MSC-secretome administered during a morphine deprivation period imposed on chronic morphine consumer UChB rats inhibited re-access morphine relapse intake by 80 to 85% (p < 0.0001). Both in the Wistar and the UChB rat models, MSCs-secretome administration reversed the morphine-induced increases in brain oxidative stress and neuroinflammation, considered as key engines perpetuating drug relapse. Overall, present preclinical studies suggest that products secreted by human mesenchymal stem cells may be of value in the treatment of opioid addictiones
dc.identifier.urihttps://doi.org/10.1038/s41398-022-02225-0es
dc.identifier.urihttp://hdl.handle.net/11447/6655
dc.language.isoenes
dc.subjectChronic Diseasees
dc.subjectEthanoles
dc.subjectMesenchymal Stem Cellses
dc.subjectMorphine / pharmacologyes
dc.subjectOpioid-Related Disorderses
dc.subjectRats, Wistares
dc.subjectRecurrencees
dc.subjectSecretomees
dc.subjectSubstance Withdrawal Syndromees
dc.titleEffect of human mesenchymal stem cell secretome administration on morphine self-administration and relapse in two animal models of opioid dependencees
dc.typeArticlees
dcterms.sourceTranslational Psychiatryes

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