@misc{10481/85208,
year = {2023},
month = {8},
url = {https://hdl.handle.net/10481/85208},
abstract = {Background: Patients with inflammatory bowel disease (IBD) have a higher risk of developing colitis-associated
colorectal cancer (CAC) with poor prognosis. IBD etiology remains undefined but involves environmental factors,
genetic predisposition, microbiota imbalance (dysbiosis) and mucosal immune defects. Mesenchymal stromal cell
(MSC) injections have shown good efficacy in reducing intestinal inflammation in animal and human studies.
However, their effect on tumor growth in CAC and their capacity to restore gut dysbiosis are not clear.
Methods: The outcome of systemic administrations of in vitro expanded human intestinal MSCs (iMSCs) on tumor
growth in vivo was evaluated using the AOM/DSS model of CAC in C57BL/6J mice. Innate and adaptive immune
responses in blood, mesenteric lymph nodes (MLNs) and colonic tissue were analyzed by flow cytometry. Intestinal
microbiota composition was evaluated by 16S rRNA amplicon sequencing.
Results: iMSCs significantly inhibited colitis and intestinal tumor development, reducing IL-6 and COX-2
expression, and IL-6/STAT3 and PI3K/Akt signaling. iMSCs decreased colonic immune cell infiltration, and
partly restored intestinal monocyte homing and differentiation. iMSC administration increased the numbers of
Tregs and IFN-γ+CD8+ T cells in the MLNs while decreasing the IL-4+Th2 response. It also ameliorated intestinal
dysbiosis in CAC mice, increasing diversity and Bacillota/Bacteroidota ratio, as well as Akkermansia abundance,
while reducing Alistipes and Turicibacter, genera associated with inflammation.
Conclusion: Administration of iMSCs protects against CAC, ameliorating colitis and partially reverting intestinal
dysbiosis, supporting the use of MSCs for the treatment of IBD.},
organization = {Instituto de Salud Carlos III
(ISCIII) (Spain)},
organization = {Project PI22/01630},
organization = {European Union},
organization = {Junta de Andalucía
(CTS 164) (Spain)},
organization = {Fondo Europeo de Desarrollo Regional
(FEDER), from the European Union},
organization = {CIBer-EHD and the
research grants PI18/00826},
organization = {P18-RT-4930, PI0206–2016},
organization = {PI19/
01058},
organization = {Spanish Ministry of Science and Innovation (“Programa de Doctorado:
Medicina Clínica y Salud Pública” B12.56.1)},
organization = {Instituto de Salud Carlos III (FI17/00176)},
organization = {Consejería de Salud, Junta de Andalucía through the
contract “Nicol´as Monardes” (C-0013–2018)},
publisher = {Elsevier},
keywords = {Mesenchymal stromal cells},
keywords = {Cell therapy},
keywords = {Colorectal cancer},
keywords = {Azoxymethane},
keywords = {DSS colitis},
keywords = {Inflammation},
keywords = {Intestinal microbiota},
keywords = {Dysbiosis},
title = {Administration of intestinal mesenchymal stromal cells reduces colitis-associated cancer in C57BL/6J mice modulating the immune response and gut dysbiosis},
doi = {10.1016/j.phrs.2023.106891},
author = {Hidalgo García, Laura and Ruiz Malagón, Antonio Jesús and Rodríguez Huertas, Jesús Francisco and Rodríguez Sojo, María Jesús and Molina Tijeras, José Alberto and Díez Echave, Patricia and Becerra, Patricia and Mirón-Pozo, Benito and Morón Romero, María Rocío and Rodríguez Nogales, Alba and Gálvez Peralta, Julio Juan and Rodríguez Cabezas, María Elena and Anderson, Per Olof},
}