EZQUER, EDUARDO MARCELO
Thumbnail Image
Preferred name
EZQUER, EDUARDO MARCELO
Main Affiliation
Email
mezquer@udd.cl
ORCID
Scopus Author ID
6508169657

Research Output

2024 2024 2023 2023 2022 2022 2021 2021 2020 2020 2019 2019 2018 2018 0.0 0.0 0.5 0.5 1.0 1.0 1.5 1.5 2.0 2.0 2.5 2.5 3.0 3.0 3.5 3.5 4.0 4.0

Filters

15
Reset filters

Settings
Now showing 1 - 10 of 15
No Thumbnail Available
Publication

Intranasal mesenchymal stem cell secretome administration markedly inhibits alcohol and nicotine self-administration and blocks relapse-intake: mechanism and translational options

2019 , María Elena Quintanilla , EZQUER, EDUARDO FERNANDO , Paola Morales , Daniela Santapau , BERRIOS CARCAMO, PABLO ANDRES , Mario Herrera-Marschitz , EZQUER, EDUARDO MARCELO , Yedy Israel

View
No Thumbnail Available
Publication

Amelioration of morphine withdrawal syndrome by systemic and intranasal administration of mesenchymal stem cell‐derived secretome in preclinical models of morphine dependence

2023 , Mauricio Quezada , Carolina Ponce , Pablo Berríos‐Cárcamo , Daniela Santapau , Javiera Gallardo , DE GREGORIO CONCHA, CRISTIAN ALEJANDRO , María Elena Quintanilla , Paola Morales , Mario Herrera‐Marschitz , EZQUER, EDUARDO MARCELO , Yedy Israel , Paula Andrés‐Herrera , Lucia Hipólito , EZQUER, EDUARDO FERNANDO

AbstractBackgroundMorphine is an opiate commonly used in the treatment of moderate to severe pain. However, prolonged administration can lead to physical dependence and strong withdrawal symptoms upon cessation of morphine use. These symptoms can include anxiety, irritability, increased heart rate, and muscle cramps, which strongly promote morphine use relapse. The morphine‐induced increases in neuroinflammation, brain oxidative stress, and alteration of glutamate levels in the hippocampus and nucleus accumbens have been associated with morphine dependence and a higher severity of withdrawal symptoms. Due to its rich content in potent anti‐inflammatory and antioxidant factors, secretome derived from human mesenchymal stem cells (hMSCs) is proposed as a preclinical therapeutic tool for the treatment of this complex neurological condition associated with neuroinflammation and brain oxidative stress.MethodsTwo animal models of morphine dependence were used to evaluate the therapeutic efficacy of hMSC‐derived secretome in reducing morphine withdrawal signs. In the first model, rats were implanted subcutaneously with mini‐pumps which released morphine at a concentration of 10 mg/kg/day for seven days. Three days after pump implantation, animals were treated with a simultaneous intravenous and intranasal administration of hMSC‐derived secretome or vehicle, and withdrawal signs were precipitated on day seven by i.p. naloxone administration. In this model, brain alterations associated with withdrawal were also analyzed before withdrawal precipitation. In the second animal model, rats voluntarily consuming morphine for three weeks were intravenously and intranasally treated with hMSC‐derived secretome or vehicle, and withdrawal signs were induced by morphine deprivation.ResultsIn both animal models secretome administration induced a significant reduction of withdrawal signs, as shown by a reduction in a combined withdrawal score. Secretome administration also promoted a reduction in morphine‐induced neuroinflammation in the hippocampus and nucleus accumbens, while no changes were observed in extracellular glutamate levels in the nucleus accumbens.ConclusionData presented from two animal models of morphine dependence suggest that administration of secretome derived from hMSCs reduces the development of opioid withdrawal signs, which correlates with a reduction in neuroinflammation in the hippocampus and nucleus accumbens.

View
No Thumbnail Available
Publication

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

2022 , María Elena Quintanilla , Mauricio Quezada , Paola Morales , BERRIOS CARCAMO, PABLO ANDRES , Mario Herrera-Marschitz , EZQUER, EDUARDO MARCELO , Daniela Santapau , Israel Yacard, Yedy , EZQUER, EDUARDO FERNANDO

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.

View
No Thumbnail Available
Publication

N-Acetylcysteine and Acetylsalicylic Acid Inhibit Alcohol Consumption by Different Mechanisms: Combined Protection

2020 , María Elena Quintanilla , EZQUER, EDUARDO FERNANDO , Paola Morales , EZQUER, EDUARDO MARCELO , OLIVARES, MARIA BELEN , Mario Herrera-Marschitz , Daniela Santapau , Yedy Israel

View
No Thumbnail Available
Publication

A dual treatment blocks alcohol binge-drinking relapse: Microbiota as a new player

2022 , EZQUER, EDUARDO FERNANDO , María Elena Quintanilla , Paola Morales , Daniela Santapau , MUNITA SEPULVEDA, JOSE MANUEL , Mario Herrera-Marschitz , EZQUER, EDUARDO MARCELO , Francisco Moya-Flores , Yedy Israel

View
No Thumbnail Available
Publication

ANTI-INFLAMMATORY MESENCHYMAL STEM CELLS AND N-ACETYL CYSTEINE INHIBIT CHRONIC ETHANOL INTAKE AND ABOLISH RELAPSE BINGE DRINKING: PRECLINICAL STUDIES

2018 , EZQUER, EDUARDO FERNANDO , EZQUER, EDUARDO MARCELO , Daniela Santapau , Yedy Israel , QUINTANILLA, M.E. , MORALES, P. , LESLAY REBOLLEDO, C. , HERRERA MARSCHITZ, M.

View
No Thumbnail Available
Publication

Chronic Voluntary Morphine Intake Is Associated with Changes in Brain Structures Involved in Drug Dependence in a Rat Model of Polydrug Use

2023 , María Elena Quintanilla , Paola Morales , Daniela Santapau , Alba Ávila , Carolina Ponce , BERRIOS CARCAMO, PABLO ANDRES , OLIVARES, MARIA BELEN , Mario Herrera-Marschitz , EZQUER, EDUARDO MARCELO , Javiera Gallardo , Yedy Israel , EZQUER, EDUARDO FERNANDO

Chronic opioid intake leads to several brain changes involved in the development of dependence, whereby an early hedonistic effect (liking) extends to the need to self-administer the drug (wanting), the latter being mostly a prefrontal–striatal function. The development of animal models for voluntary oral opioid intake represents an important tool for identifying the cellular and molecular alterations induced by chronic opioid use. Studies mainly in humans have shown that polydrug use and drug dependence are shared across various substances. We hypothesize that an animal bred for its alcohol preference would develop opioid dependence and further that this would be associated with the overt cortical abnormalities clinically described for opioid addicts. We show that Wistar-derived outbred UChB rats selected for their high alcohol preference additionally develop: (i) a preference for oral ingestion of morphine over water, resulting in morphine intake of 15 mg/kg/day; (ii) marked opioid dependence, as evidenced by the generation of strong withdrawal signs upon naloxone administration; (iii) prefrontal cortex alterations known to be associated with the loss of control over drug intake, namely, demyelination, axonal degeneration, and a reduction in glutamate transporter GLT-1 levels; and (iv) glial striatal neuroinflammation and brain oxidative stress, as previously reported for chronic alcohol and chronic nicotine use. These findings underline the relevance of polydrug animal models and their potential in the study of the wide spectrum of brain alterations induced by chronic morphine intake. This study should be valuable for future evaluations of therapeutic approaches for this devastating condition.

View
No Thumbnail Available
Publication

Aspirin and N‐acetylcysteine co‐administration markedly inhibit chronic ethanol intake and block relapse binge drinking: Role of neuroinflammation‐oxidative stress self‐perpetuation

2019 , Yedy Israel , María Elena Quintanilla , EZQUER, EDUARDO FERNANDO , Paola Morales , Daniela Santapau , BERRIOS CARCAMO, PABLO ANDRES , EZQUER, EDUARDO MARCELO , OLIVARES, MARIA BELEN , Mario Herrera‐Marschitz

View
No Thumbnail Available
Publication

Human adipose-derived mesenchymal stem cell-conditioned medium ameliorates polyneuropathy and foot ulceration in diabetic BKS db/db mice

2020 , DE GREGORIO CONCHA, CRISTIAN ALEJANDRO , CONTADOR MARTINEZ, DAVID ERNESTO , Cristian Acosta , Diego Díaz , Constanza Cárcamo , Daniela Santapau , Lorena Lobos-Gonzalez , Mario Campero , Daniel Carpio , Caterina Gabriele , Marco Gaspari , Victor Aliaga-Tobar , Vinicius Maracaja-Coutinho , EZQUER, EDUARDO MARCELO , EZQUER, EDUARDO FERNANDO

Abstract Background Diabetic polyneuropathy (DPN) is the most common and early developing complication of diabetes mellitus, and the key contributor for foot ulcers development, with no specific therapies available. Different studies have shown that mesenchymal stem cell (MSC) administration is able to ameliorate DPN; however, limited cell survival and safety reasons hinder its transfer from bench to bedside. MSCs secrete a broad range of antioxidant, neuroprotective, angiogenic, and immunomodulatory factors (known as conditioned medium), which are all decreased in the peripheral nerves of diabetic patients. Furthermore, the abundance of these factors can be boosted in vitro by incubating MSCs with a preconditioning stimulus, enhancing their therapeutic efficacy. We hypothesize that systemic administration of conditioned medium derived from preconditioned MSCs could reverse DPN and prevent foot ulcer formation in a mouse model of type II diabetes mellitus. Methods Diabetic BKS db/db mice were treated with systemic administration of conditioned medium derived from preconditioned human MSCs; conditioned medium derived from non-preconditioned MSCs or vehicle after behavioral signs of DPN was already present. Conditioned medium or vehicle administration was repeated every 2 weeks for a total of four administrations, and several functional and structural parameters characteristic of DPN were evaluated. Finally, a wound was made in the dorsal surface of both feet, and the kinetics of wound closure, re-epithelialization, angiogenesis, and cell proliferation were evaluated. Results Our molecular, electrophysiological, and histological analysis demonstrated that the administration of conditioned medium derived from non-preconditioned MSCs or from preconditioned MSCs to diabetic BKS db/db mice strongly reverts the established DPN, improving thermal and mechanical sensitivity, restoring intraepidermal nerve fiber density, reducing neuron and Schwann cell apoptosis, improving angiogenesis, and reducing chronic inflammation of peripheral nerves. Furthermore, DPN reversion induced by conditioned medium administration enhances the wound healing process by accelerating wound closure, improving the re-epithelialization of the injured skin and increasing blood vessels in the wound bed in a skin injury model that mimics a foot ulcer. Conclusions Studies conducted indicate that MSC-conditioned medium administration could be a novel cell-free therapeutic approach to reverse the initial stages of DPN, avoiding the risk of lower limb amputation triggered by foot ulcer formation and accelerating the wound healing process in case it occurs.

View
No Thumbnail Available
Publication

Methadone directly impairs central nervous system cells in vitro

2024 , Cristian De Gregorio , Javiera Gallardo , BERRIOS CARCAMO, PABLO ANDRES , Álex Handy , Daniela Santapau , ANTONIA GONZALEZ MADRID , EZQUER, EDUARDO MARCELO , Paola Morales , Alejandro Luarte , Daniela Corvalán , Úrsula Wyneken , EZQUER, EDUARDO FERNANDO

View