Improved efficacy of mesenchymal stromal cells stably expressing CXCR4 and IL-10 in a xenogeneic graft versus host disease mouse model.

Autor:	Hervás-Salcedo R; Hematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.; Advanced Therapies Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT)/Instituto de Investigación Sanitaria (IIS) Fundación Jiménez Díaz, Madrid, Spain., Fernández-García M; Hematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.; Advanced Therapies Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT)/Instituto de Investigación Sanitaria (IIS) Fundación Jiménez Díaz, Madrid, Spain., Hernando-Rodríguez M; Hematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.; Advanced Therapies Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT)/Instituto de Investigación Sanitaria (IIS) Fundación Jiménez Díaz, Madrid, Spain., Suárez-Cabrera C; Translational Oncology Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Centro de Investigación Biomédica en Red de 8 Cancer (CIBERONC), Madrid, Spain.; Biomedical Research Institute I + 12, Hospital 12 de Octubre, Madrid, Spain., Bueren JA; Hematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.; Advanced Therapies Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT)/Instituto de Investigación Sanitaria (IIS) Fundación Jiménez Díaz, Madrid, Spain., Yáñez RM; Hematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.; Advanced Therapies Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT)/Instituto de Investigación Sanitaria (IIS) Fundación Jiménez Díaz, Madrid, Spain.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Feb 01; Vol. 14, pp. 1062086. Date of Electronic Publication: 2023 Feb 01 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1062086
Abstrakt:	Previous clinical trials have shown that mesenchymal stromal cells (MSCs) can modulate graft versus host disease (GvHD) after allogeneic hematopoietic transplantation, although with variable efficacy. To improve the anti-GvHD effect of these cells, adipose tissue derived-human MSCs (Ad-MSCs) were transduced with a lentiviral vector conferring stable expression of CXCR4, a molecule involved in cell migration to inflamed sites, and IL-10, a cytokine with potent anti-inflammatory properties. In vitro experiments showed that the expression of these molecules in Ad-MSCs (named CXCR4-IL10-MSCs) efficiently enhanced their migration towards SDF-1α and also improved their immunomodulatory properties compared to unmodified Ad-MSCs (WT-MSCs). Moreover, using a humanized GvHD mouse model, CXCR4-IL10-MSCs showed improved therapeutic effects, which were confirmed by histopathologic analysis in the target organs. Additionally, compared to WT-MSCs, CXCR4-IL10-MSCs induced a more marked reduction in the number of pro-inflammatory Th1 and Th17 cells, a higher polarization towards an anti-inflammatory T cell profile (CD3 + -IL10 + cells), and increased the number of regulatory T and B cells. Our in vitro and in vivo studies strongly suggest that CXCR4-IL10-MSCs should constitute an important new generation of MSCs for the treatment of GvHD in patients transplanted with allogeneic hematopoietic grafts. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Hervás-Salcedo, Fernández-García, Hernando-Rodríguez, Suárez-Cabrera, Bueren and Yáñez.)
Databáze:	MEDLINE
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