Guía de uso adecuado de modelos animales para el desarrollo de terapias en esclerosis múltiple

Moreno, Beatriz; Espejo, Carmen; Mestre, Leyre; Suardíaz, Margarita; Clemente, Diego; Castro, Fernando de; Fernández-Fernández, Óscar; Montalbán, X; Villoslada, Pablo; Guaza, Carmen

doi:10.33588/rn.5402.2011424

Cited by 4 publications

(2 citation statements)

References 48 publications

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“…We used the EAE murine model, which is widely used to study the autoimmune aspects of MS 33‐35 . This model involves the auto‐immune processes that ends in a demyelinating process along the CNS to induce in mice a MS model that involves autoimmune response.…”

Section: Methodsmentioning

confidence: 99%

“…We used the EAE murine model, which is widely used to study the autoimmune aspects of MS. 33 , 34 , 35 This model involves the auto‐immune processes that ends in a demyelinating process along the CNS to induce in mice a MS model that involves autoimmune response. In short, at Day 0, 6‐ to 8‐week‐old C57Bl6 female mice were anesthetized with xylazine (20 mg/mL) and ketamine (37 mg/kg).…”

Section: Methodsmentioning

confidence: 99%

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Efficacy of a benzothiazole‐based LRRK2 inhibitor in oligodendrocyte precursor cells and in a murine model of multiple sclerosis

Benítez‐Fernández,

Josa‐Prado,

Sánchez

et al. 2024

CNS Neurosci Ther

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AimsMultiple sclerosis (MS) is a chronic neurological disease that currently lacks effective curative treatments. There is a need to find effective therapies, especially to reverse the progressive demyelination and neuronal damage. Oligodendrocytes form the myelin sheath around axons in the central nervous system (CNS) and oligodendrocyte precursor cells (OPCs) undergo mechanisms that enable spontaneously the partial repair of damaged lesions. The aim of this study was to discover small molecules with potential effects in demyelinating diseases, including (re)myelinating properties.MethodsRecently, it has been shown how LRRK2 inhibition promotes oligodendrogliogenesis and therefore an efficient repair or myelin damaged lesions. Here we explored small molecules inhibiting LRRK2 as potential enhancers of primary OPCs proliferation and differentiation, and their potential impact on the clinical score of experimental autoimmune encephalomyelitys (EAE) mice, a validated model of the most frequent clinical form of MS, relapsing–remitting MS.ResultsOne of the LRRK2 inhibitors presented in this study promoted the proliferation and differentiation of OPC primary cultures. When tested in the EAE murine model of MS, it exerted a statistically significant reduction of the clinical burden of the animals, and histological evidence revealed how the treated animals presented a reduced lesion area in the spinal cord.ConclusionsFor the first time, a small molecule with LRRK2 inhibition properties presented (re)myelinating properties in primary OPCs cultures and potentially in the in vivo murine model. This study provides an in vivo proof of concept for a LRRK2 inhibitor, confirming its potential for the treatment of MS.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Efficacy of a benzothiazole‐based LRRK2 inhibitor in oligodendrocyte precursor cells and in a murine model of multiple sclerosis

Benítez‐Fernández,

Josa‐Prado,

Sánchez

et al. 2024

CNS Neurosci Ther

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Models for Studying Myelination, Demyelination and Remyelination

et al. 2017

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One of the most widely studied demyelinating diseases is multiple sclerosis, which is characterised by the appearance of demyelinating plaques, followed by myelin regeneration. Nevertheless, with disease progression, remyelination tends to fail, increasing the characteristic neurodegeneration of the disease. It is essential to understand the mechanisms that operate in the processes of myelination, demyelination and remyelination to develop treatments that promote the production of new myelin, thereby protecting the central nervous system. A huge variety of models have been developed to help improve our understanding of these processes. Nevertheless, no single model allows us to study all the processes involved in remyelination and usually more than one is needed to provide a full picture of related mechanisms. In this review, we summarise the most commonly used models for studying myelination, demyelination and remyelination and we analyse them critically to outline the most suitable ways of using them.

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Mesenchymal properties of SJL mice-stem cells and their efficacy as autologous therapy in a relapsing–remitting multiple sclerosis model

et al. 2014

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IntroductionMesenchymal stem cells (MSCs) are a multipotent population of adult stem cells, which may represent a promising therapeutic approach for neurological autoimmune diseases such as multiple sclerosis. The mouse is the most used species for obtaining and studying the characteristics of MSC and their potential as autologous transplants in pre-clinical models. However, conflicting data have been published disclosing intraspecies variations. The choice of the mouse strain and the tissue source appear, among others, as important factors in the experimental application of MSCs.MethodsAdipose tissue-derived MSCs obtained from the SJL/JCrl mouse strain (SJL-AdMSC) have been cultured for a long time (from passage 0 up to 15) under controlled experimental conditions, and their growth rate, morphology, stromal and haematopoietic marker expression profiles and differentiation capacity towards adipocytes, osteocytes and chondrocytes have been determined. Moreover, their preclinical efficacy has been assessed by autologous transplant in relapsing-remitting experimental autoimmune encephalomielitis (RR-EAE)-induced SJL mice (a well established mice model for the study of RR-multiple sclerosis).ResultsWe demonstrate that SJL-AdMSCs show the same fibroblastic shape, growth rate, profile of markers expression and multipotency described for MSCs in every passage evaluated (up to passage 15). Additionally, SJL-AdMSCs ameliorate the RR-EAE course, suggesting that they could modulate disease progression. Moreover, their features studied are fully comparable with the standardized Ad-MSCs obtained from the C57BL/6 mouse strain, which strengthens their use in cell therapy.ConclusionSJL-AdMSCs might be a suitable source of Ad-MSCs for studies related to the properties of MSCs and their application as promising therapeutic tools in autologous transplants in experimental medicine.

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Guía de uso adecuado de modelos animales para el desarrollo de terapias en esclerosis múltiple

Abstract: F, et al. Guía de uso adecuado de modelos animales para el desarrollo de terapias en esclerosis múltiple.

Cited by 4 publications

References 48 publications

Efficacy of a benzothiazole‐based LRRK2 inhibitor in oligodendrocyte precursor cells and in a murine model of multiple sclerosis

Efficacy of a benzothiazole‐based LRRK2 inhibitor in oligodendrocyte precursor cells and in a murine model of multiple sclerosis

Models for Studying Myelination, Demyelination and Remyelination

Mesenchymal properties of SJL mice-stem cells and their efficacy as autologous therapy in a relapsing–remitting multiple sclerosis model

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