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

Frontiers in Immunology

Immunology

Rosario Hervás-Salcedo¹  Juan A. Bueren¹  Miriam Hernando-Rodríguez¹  María Fernández-García¹  Rosa M. Yáñez¹  Cristian Suárez-Cabrera² 

[1] 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;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;

关键词: mesenchymal stromal cells;    graft vs host disease;    CXCR4;    IL10;    stem cell therapy;    immunomodulation;    lentiviral vector;   

DOI  :  10.3389/fimmu.2023.1062086

 received in 2022-10-05, accepted in 2023-01-04,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

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Copyright © 2023 Hervás-Salcedo, Fernández-García, Hernando-Rodríguez, Suárez-Cabrera, Bueren and Yáñez