{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:34:53Z","timestamp":1787009693220,"version":"build-2736575974"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T00:00:00Z","timestamp":1646265600000},"content-version":"vor","delay-in-days":61,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000008","name":"Health Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000008","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Spanish Ministry of Science and Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Spanish Association of Cancer Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mesenchymal 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 \u201csuicide gene\u201d 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 \u201cparental\u201d 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.<\/jats:p>","DOI":"10.1093\/stcltm\/szab007","type":"journal-article","created":{"date-parts":[[2021,12,31]],"date-time":"2021-12-31T23:49:14Z","timestamp":1640994554000},"page":"88-96","source":"Crossref","is-referenced-by-count":12,"title":["Robust In Vitro and In Vivo Immunosuppressive and Anti-inflammatory Properties of Inducible Caspase-9-mediated Apoptotic Mesenchymal Stromal\/Stem Cell"],"prefix":"10.1093","volume":"11","author":[{"given":"Paola Alejandra","family":"Romec\u00edn","sequence":"first","affiliation":[{"name":"Josep Carreras Leukemia Research Institute, Barcelona, Spain"},{"name":"RICORS-TERAV, ISCIII, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meritxell","family":"Vinyoles","sequence":"additional","affiliation":[{"name":"Josep Carreras Leukemia Research Institute, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bel\u00e9n","family":"L\u00f3pez-Mill\u00e1n","sequence":"additional","affiliation":[{"name":"Josep Carreras Leukemia Research Institute, Barcelona, Spain"},{"name":"RICORS-TERAV, ISCIII, Madrid, Spain"},{"name":"GENYO, Centro Pfizer-Universidad de Granada-Junta de Andaluc\u00eda de Gen\u00f3mica e Investigaci\u00f3n Oncol\u00f3gica, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Diaz","family":"de la Guardia","sequence":"additional","affiliation":[{"name":"GENYO, Centro Pfizer-Universidad de Granada-Junta de Andaluc\u00eda de Gen\u00f3mica e Investigaci\u00f3n Oncol\u00f3gica, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noemi M","family":"Atucha","sequence":"additional","affiliation":[{"name":"Departamento de Fisiologia Humana, Facultad de Medicina, Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergi","family":"Querol","sequence":"additional","affiliation":[{"name":"RICORS-TERAV, ISCIII, Madrid, Spain"},{"name":"Banc de Sang i Teixits, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Bueno","sequence":"additional","affiliation":[{"name":"Josep Carreras Leukemia Research Institute, Barcelona, Spain"},{"name":"RICORS-TERAV, ISCIII, Madrid, Spain"},{"name":"CIBERONC, ISCIII, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Benitez","sequence":"additional","affiliation":[{"name":"Instituto de Parasitologia y Biomedicina L\u00f3pez-Neyra (IPBLN-CSIC), Armilla, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Gonzalez-Rey","sequence":"additional","affiliation":[{"name":"Instituto de Parasitologia y Biomedicina L\u00f3pez-Neyra (IPBLN-CSIC), Armilla, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Delgado","sequence":"additional","affiliation":[{"name":"Instituto de Parasitologia y Biomedicina L\u00f3pez-Neyra (IPBLN-CSIC), Armilla, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Men\u00e9ndez","sequence":"additional","affiliation":[{"name":"Josep Carreras Leukemia Research Institute, Barcelona, Spain"},{"name":"RICORS-TERAV, ISCIII, Madrid, Spain"},{"name":"CIBERONC, ISCIII, Barcelona, Spain"},{"name":"Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats (ICREA), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,3,3]]},"reference":[{"issue":"4","key":"2022030315095339700_CIT0001","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1097\/00007890-197404000-00001","article-title":"Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo.","volume":"17","author":"Friedenstein","year":"1974","journal-title":"Transplantation"},{"key":"2022030315095339700_CIT0002","doi-asserted-by":"crossref","first-page":"107836","DOI":"10.1155\/2012\/107836","article-title":"Amniotic fluid and amniotic membrane stem cells: marker discovery.","volume":"2012","author":"Roubelakis","year":"2012","journal-title":"Stem Cells Int"},{"issue":"9","key":"2022030315095339700_CIT0003","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1111\/j.1365-2591.2011.01877.x","article-title":"Mesenchymal stem cells derived from dental tissues.","volume":"44","author":"Rodr\u00edguez-Lozano","year":"2011","journal-title":"Int Endod J"},{"issue":"416","key":"2022030315095339700_CIT0004","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aam7828","article-title":"Apoptosis in mesenchymal stromal cells induces in vivo recipient-mediated immunomodulation.","volume":"9","author":"Galleu","year":"2017","journal-title":"Sci. Trans. 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