Robust in Vitro and in Vivo Immunosuppressive and Anti-inflammatory Properties of Inducible Caspase-9-mediated Apoptotic Mesenchymal Stromal/Stem Cell
Romecín, Paola Alejandra (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Vinyoles, Meritxell (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
López-Millán, Belén (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Díaz de la Guardia, Rafael (GENYO. Centro Pfizer-Universidad de Granada-Junta de Andalucia de Genomica e Investigacion Oncologica)
Atucha, Noemí M. (Universidad de Murcia)
Querol, Sergi (Banc de Sang i Teixits)
Bueno, Clara (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Benitez, Raquel (Instituto de Parasitología y Biomedicina "López-Neyra")
Gonzalez-Rey, Elena (Instituto de Parasitología y Biomedicina "López-Neyra")
Delgado, Mario (Instituto de Parasitología y Biomedicina "López-Neyra")
Menéndez Bujan, Pablo (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)

Fecha:	2022
Resumen:	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 "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.
Ayudas:	Ministerio de Ciencia e Innovación IJCI-2017-3317
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	BM-MSC ; WJ-MSC ; ICasp9 switch ; Immunosuppression ; Anti-inflammatory ; Colitis in vivo model
Publicado en:	Stem Cells Translational Medicine, Vol. 11 Núm. 1 (march 2022) , p. 88-96, ISSN 2157-6580

DOI: 10.1093/stcltm/szab007
PMID: 35641173

9 p, 21.0 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Instituto de Investigación contra la Leucemia Josep Carreras
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