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Robust In vitro and in vivo immunosuppressive and anti-inflammatory properties of Inducible caspase-9-mediated apoptotic mesenchymal stromal/stem cell

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dc.contributor.authorRomecín, Paola Alejandra
dc.contributor.authorVinyoles, Meritxell
dc.contributor.authorLópez-Millán, Belén
dc.contributor.authorDiaz de la Guardia, Rafael
dc.contributor.authorMarín Atucha, Noemí
dc.contributor.authorQuerol, Sergi
dc.contributor.authorBueno, Clara
dc.contributor.authorBenitez, Raquel
dc.contributor.authorGonzález-Rey, Elena
dc.contributor.authorDelgado, Mario
dc.contributor.authorMenéndez, Pablo
dc.contributor.departmentFisiología
dc.contributor.otherFacultad de Medicina
dc.date.accessioned2026-01-21T08:33:58Z
dc.date.available2026-01-21T08:33:58Z
dc.date.copyright© 2022, The Authors
dc.date.issued2022-03-03
dc.description.abstractMesenchymal stromal stem/cells (MSC) therapies are clinically used in a wide range of disorders based on their robust HLA-independent immunosuppressive and anti-inflammatory properties. However, the mechanisms underlying MSC therapeutic activity remain elusive as demonstrated by the unpredictable therapeutic efficacy of MSC infusions reported in multiple clinical trials. A seminal recent study showed that infused MSCs are actively induced to undergo apoptosis by recipient cytotoxic T cells, a mechanism that triggers in vivo recipient-induced immunomodulation by such apoptotic MSCs, and the need for such recipient cytotoxic cell activity could be replaced by the administration of ex vivo-generated apoptotic MSCs. Moreover, the use of MSC-derived extracellular vesicles (MSC-EVs) is being actively explored as a cell-free therapeutic alternative over the parental MSCs. We hypothesized that the introduction of a "suicide gene" switch into MSCs may offer on-demand in vivo apoptosis of transplanted MSCs. Here, we prompted to investigate the utility of the iCasp9/AP1903 suicide gene system in inducing apoptosis of MSCs. iCasp9/AP1903-induced apoptotic MSCs (MSCiCasp9+) were tested in vitro and in in vivo models of acute colitis. Our data show a very similar and robust immunosuppressive and anti-inflammatory properties of both "parental" alive MSCGFP+ cells and apoptotic MSCiCasp9+ cells in vitro and in vivo regardless of whether apoptosis was induced in vivo or in vitro before administering MSCiCasp9+ lysates. This development of an efficient iCasp9 switch may potentiate the safety of MSC-based therapies in the case of an adverse event and, will also circumvent current logistic technical limitations and biological uncertainties associated to MSC-EVs.
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dc.format.extent9
dc.identifier.citationStem Cells Transl Med. 2022 Mar 3;11(1):88-96
dc.identifier.doihttps://doi.org/10.1093/stcltm/szab007
dc.identifier.urihttp://hdl.handle.net/10201/189689
dc.languageeng
dc.publisherOxford University Press
dc.relationThe financial support for this work was obtained from Health Canada (H4080-144541) to P.M. M.V. and B.L.-M. were supported by a Juan de la Cierva fellowship by the Spanish Ministry of Science and Innovation (IJCI-2017-3317) and a fellowship from the Spanish Association of Cancer Research (AECC), respectively.
dc.relation.publisherversionhttps://academic.oup.com/stcltm/article/11/1/88/6541839
dc.rightsAttribution 4.0 International*
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectWJ-MSC
dc.subjectAnti-inflammatory
dc.subjectColitis in vivo model
dc.subjectiCasp9 switch
dc.subjectImmunosuppression
dc.subjectBM-MSC
dc.subject.odsObjetivo 3: Salud
dc.titleRobust In vitro and in vivo immunosuppressive and anti-inflammatory properties of Inducible caspase-9-mediated apoptotic mesenchymal stromal/stem cell
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublicationes
relation.isAuthorOfPublication65436b53-1614-4a88-8c35-626a1d4c31ae
relation.isAuthorOfPublication.latestForDiscovery65436b53-1614-4a88-8c35-626a1d4c31ae
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