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

Journal
Translational Psychiatry
ISSN
2158-3188
Date Issued
2022
Author(s)
María Elena Quintanilla
Mauricio Quezada
Paola Morales
Mario Herrera-Marschitz
Daniela Santapau
Israel Yacard, Yedy
Type
Resource Types::text::journal::journal article
Scopus ID
2-s2.0-85141158210
WoS ID
WOS:000879029800001
DOI
URL
URL Institutional Repository
Abstract
<jats:title>Abstract</jats:title><jats:p>The 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%; <jats:italic>p</jats:italic> < 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.</jats:p>
Cite this document
Quintanilla, M. E., Quezada, M., Morales, P., Berríos-Cárcamo, P., Santapau, D., Ezquer, M., Herrera-Marschitz, M., Israel, Y., & Ezquer, F. (2022). Effect of human mesenchymal stem cell secretome administration on morphine self-administration and relapse in two animal models of opioid dependence. Translational Psychiatry, 12(1), 462. https://doi.org/10.1038/s41398-022-02225-0
Project(s)
Subjects
animals

; 

chronic disease

; 

ethanol

; 

humans

; 

mesenchymal stem cells

; 

models, animal

; 

morphine

; 

opioid-related disorders

; 

rats

; 

rats, wistar

; 

recurrence

; 

secretome

; 

substance withdrawal syndrome

; 

water

; 

alcohol

; 

glutamate transporter

; 

morphine

; 

naloxone

; 

opiate receptor

; 

water

; 

morphine

; 

adipose tissue

; 

animal cell

; 

animal experiment

; 

animal model

; 

article

; 

controlled study

; 

drug self administration

; 

male

; 

mesenchymal stem cell

; 

morphine addiction

; 

mrna expression level

; 

nonhuman

; 

oxidative stress

; 

rat

; 

relapse

; 

secretome

; 

wistar rat

; 

withdrawal syndrome

; 

animal

; 

chronic disease

; 

human

; 

opiate addiction

; 

recurrent disease

; 

withdrawal syndrome