De novo interleukin-10 production primed by Lactobacillus sakei CVL-001 amplifies the immunomodulatory abilities of mesenchymal stem cells to alleviate colitis.

Abstract

Mesenchymal stem cells (MSCs) hold therapeutic promise for treating inflammatory bowel disease (IBD) owing to their immunomodulatory properties. Currently, pre-conditioning strategies with several beneficial agents have been applied to enhance the efficacy of MSCs in treating IBDs. Probiotics are increasingly acknowledged as supplemental therapy for IBD; however, their potential benefits in MSCs-based therapy remain largely unexplored. In this study, we hypothesized that pretreating MSCs with Lactobacillus sakei CVL-001 (L. sakei CVL-001), a representative probiotic strain, could improve their therapeutic effectiveness for IBD. In line with this hypothesis, we noted that pretreatment with L. sakei CVL-001 significantly induced IL-10 secretion in MSCs via the activation of the STAT3 signaling pathway. These primed MSCs reduced pro-inflammatory cytokine production in LPS/IFN-γ-treated macrophages and promoted an M2 phenotype, associated with immunoregulation and tissue repair, in undifferentiated macrophages. In addition, their conditioned media significantly reduced the proliferation capacity of Jurkat T cells and splenocytes, while the neutralization of IL-10 reversed these phenomena. Furthermore, MSCs treated with L. sakei CVL-001 mitigated inflammatory responses and promoted epithelial regeneration, leading to accelerated recovery from disease symptoms and improved survival rates compared to naive MSCs in a DSS-induced colitis mouse model. In conclusion, our findings suggest that probiotics, such as L. sakei CVL-001, can improve the therapeutic efficacy of MSCs for treating IBD.