OPTIMISATION OF THE TREATMENT OF ACUTE GVHD WITH STROMAL MESENCHYMAL CELLS OF ADIPOCYTIC ORIGIN (Q3161222)

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Revision as of 17:21, 12 October 2021 by DG Regio (talk | contribs) (‎Created claim: summary (P836): Allogeneic transplantation is the only therapeutic option for many patients with malignant haemopathies. Its results are limited by its high toxicity, with graft-versus-host disease (GHD) being the main cause of morbidity and mortality. GVHD occurs in 30-70 % of patients; of these up to 80 % do not respond or relapse after first line of treatment (corticoids), and their survival does not exceed 15 % in most studies. Mesenchymal stromal cells (MS...)
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Project Q3161222 in Spain
Language Label Description Also known as
English
OPTIMISATION OF THE TREATMENT OF ACUTE GVHD WITH STROMAL MESENCHYMAL CELLS OF ADIPOCYTIC ORIGIN
Project Q3161222 in Spain

    Statements

    contained in NUTS
    Navarre
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    country
    Spain
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    EU contribution
    14,375.0 Euro
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    budget
    28,750.0 Euro
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    co-financing rate
    50.0 percent
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    start time
    1 January 2014
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    end time
    31 March 2018
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    beneficiary name (string)
    UNIVERSIDAD DE NAVARRA
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    coordinate location

    42°49'6.42"N, 1°38'39.34"W
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    postal code
    31201
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    summary
    El trasplante alogénico constituye la única opción terapéutica para numerosos pacientes con hemopatías malignas. Sus resultados se ven limitados por su elevada toxicidad, siendo la enfermedad injerto contra huésped (EICH) la principal causa de morbi-mortalidad. La EICH se produce en 30-70% de los pacientes; de ellos hasta un 80% no responden o recaen tras primera línea de tratamiento (corticoides), y su supervivencia no supera el 15% en la mayoría de estudios. Las células estromales mesenquimales (MSCs) se han empleado con resultados dispares en el tratamiento de la EICH aguda. Algunos miembros de este Consorcio han desarrollado dos ensayos clínicos previos en los que demostraron que: 1. es posible utilizar en clínica MSCs expandidas a partir de médula ósea en ausencia de suero bovino, lo que evitan potenciales riesgos de zoonosis y 2. dado que el efecto de las MSCs sobre el sistema inmune es transitorio, la administración secuencial de MSCs puede aumentar su eficacia. En este sentido, se desconoce cuál es la mejor pauta de administración o cuál es la mejor fuente de MSCs, que pueden aislarse también fácilmente a partir de tejido adiposo (lipoaspirados, que normalmente se desechan) (Ad-MSCs). Finalmente, tras su infusión, las MSCs desparecen rápidamente, por lo que será importante aumentar su eficacia terapéutica mediante mecanismos que favorezcan su migración y efecto inmunosupresor en órganos diana de la EICH. Para ello se desarrollarán diversas estrategias entre las que se incluyen la fucosilación o sobre-expresión de moléculas de adhesión y/o inmunosupresoras mediante transferencia de mRNAs o tratamientos farmacológicos de las MSCs. La eficacia de estos procesos de manipulación de las MSCs sobre la EICH permitirá extrapolar su aplicación a otras enfermedades inflamatorias y autoinmunes de alta incidencia en la población y con pocas opciones terapéuticas eficaces. (Spanish)
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    Allogeneic transplantation is the only therapeutic option for many patients with malignant haemopathies. Its results are limited by its high toxicity, with graft-versus-host disease (GHD) being the main cause of morbidity and mortality. GVHD occurs in 30-70 % of patients; of these up to 80 % do not respond or relapse after first line of treatment (corticoids), and their survival does not exceed 15 % in most studies. Mesenchymal stromal cells (MSCs) have been used with mixed results in the treatment of acute GVHD. Some members of this Consortium have developed two previous clinical trials in which they demonstrated that: 1. It is possible to use in clinic MSCs expanded from bone marrow in the absence of bovine serum, which avoids potential risks of zoonoses and 2. since the effect of MSCs on the immune system is transient, sequential administration of MSCs may increase their efficacy. In this sense, it is unknown which is the best administration pattern or which is the best source of MSCs, which can also be easily isolated from adipose tissue (lipoaspirates, usually discarded) (Ad-MSCs). Finally, after infusion, MSCs disappear quickly, so it will be important to increase their therapeutic efficacy through mechanisms that favor their migration and immunosuppressive effect on target organs of GVHD. To this end, various strategies will be developed, including fucosylation or over-expression of adhesion or immunosuppressive molecules through mRNA transfer or pharmacological treatments of MSCs. The effectiveness of these processes of manipulation of MSCs on GVHD will make it possible to extrapolate their application to other inflammatory and autoimmune diseases of high incidence in the population and with few effective therapeutic options. (English)
    point in time
    12 October 2021
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    location (string)
    Pamplona/Iruña
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    Identifiers

    Spanish Kohesio ID
    PI13_02188
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