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

Abstract

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.

Combination of bone marrow mesenchymal stem cells and moxibustion restores cyclophosphamide-induced premature ovarian insufficiency by improving mitochondrial function and regulating mitophagy

“…Enhancing Sdf1 and Cxcr4 expression has been shown to promote the mobilization and homing of MSCs. While viral transduction, drug pretreatment, and gene editing are important methods to explore in promoting expression of Sdf1 and Cxcr4 , they may not currently be feasible in clinical practice [ 12 , 43 , 44 ]. Moxibustion, an external treatment used in traditional Chinese medicine, is popular in clinical practice and is easy to use.…”

“…Mesenchymal stem cells (MSCs) have emerged as potential therapeutic candidates for ovarian aging [ 10 , 11 ]. A recent study provided clinical evidence that substantiated the effects of MSCs in improving ovarian response, pregnancy rate, and live birth rate [ 12 ]. Bone marrow mesenchymal stem cells (BMSCs) are advantageous owing to their easy accessibility and low immunogenicity [ 13 , 14 ].…”

Bioengineered Mesenchymal Stem/Stromal Cells in Anti-Cancer Therapy: Current Trends and Future Prospects

“…Overexpression of other chemokine receptors such as CXCR7 or the α4 chain of VLA-4 integrin, has demonstrated an improved MSC homing to inflamed/injured tissues [53,54]. Levy et al aimed to enhance the ability of MSCs to tether and roll over endothelium by transfecting these cells with mRNA for PSGL-1 and sialyl Lewis X (sLeX), which are ligands for P-and E-/L-selectin, respectively [55], while Hervás-Salcedo et al showed that the transient expression of CXCR4 by mRNA transfection improved MSC migration to inflamed tissues [56].…”

A Stacking Machine Learning Method for IL-10-Induced Peptide Sequence Recognition Based on Unified Deep Representation Learning

“…Interleukin-10 (IL-10), a pleiotropic cell-signaling cytokine, contributes to immune modulation and inflammation [1]. Its production occurs in various lymphocyte subtypes, including macrophages, B cells, granulocytes, dendritic cells, and multiple T cell subsets [2,3].…”