@misc{10481/74049,
year = {2022},
month = {3},
url = {http://hdl.handle.net/10481/74049},
abstract = {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 cellfree
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.},
organization = {Health Canada	H4080-144541},
organization = {Juan de la Cierva fellowship by the Spanish Ministry of Science and Innovation	IJCI-2017-3317},
organization = {Spanish Association of Cancer Research (AECC)},
publisher = {Oxford University Press},
keywords = {BM-MSC},
keywords = {WJ-MSC},
keywords = {iCasp9 switch},
keywords = {Immunosuppression},
keywords = {Anti-inflammatory},
keywords = {Colitis in vivo model},
title = {Robust In Vitro and In Vivo Immunosuppressive and Anti-inflammatory Properties of Inducible Caspase-9- mediated Apoptotic Mesenchymal Stromal/Stem Cell},
doi = {10.1093/stcltm/szab007},
author = {Romecín, Paola Alejandra and López Millán, María Belén and Díaz de la Guardia Quiles, Rafael and Benítez, Raquel and González Rey, Elena and Delgado, Mario},
}