Mesenchymal stromal cell-derived membrane particles: A novel cell-free therapy for inflammatory bowel diseases

• DOI: 10.1016/j.intimp.2023.110076
• Publication Date: 2023-04-06T17:16:02Z
• Authors: Michele Aramburu ...; Dienifer Hermann ...; Ana Beatriz Titto...; Monique Franco-da...; Mariana Rauback A...; Tuane Nerissa Alv...; Anelise Araújo; Fernanda dos Sant...; Martin J. Hoogduijn; Fabiany da Costa ...; Ana Helena Paz
• Keywords: Mice, Inbred C57BL; Inflammation; Mice; Disease Models, Animal; Colon; Culture Media, Conditioned; Dextran Sulfate; Animals; Cytokines; Mesenchymal Stem Cells; Inflammatory Bowel Diseases; Colitis; 3. Good health

Inflammatory bowel diseases (IBD), including ulcerative colitis, are chronic and idiopathic inflammations of the gastrointestinal tract. A disruption of the epithelial barrier and an imbalance between Th1 and Th2 subsets are associated with the onset and progression of these diseases. Mesenchymal stromal cells (MSC) are a promising therapy for IBD. However, cell-tracking studies have shown that intravenously infused MSC localize to the lungs and present short-term survival. To reduce practical complexities arising from living cells, we generated membrane particles (MP) from MSC membranes, which possess some of the immunomodulatory properties of MSC. This study investigated the effect of MSC-derived MP and conditioned media (CM) as cell-free therapies in the dextran sulfate sodium (DSS)-induced colitis model. Acute colitis was induced in C57BL/6 mice by oral administration of 2% DSS in drinking water ad libitum from days 0 to 7. Mice were treated with MP, CM, or living MSC on days 2 and 5. Our findings revealed that MP, CM, and living MSC ameliorated DSS-induced colitis by reducing colonic inflammation, the loss of colonic goblet cells, and intestinal mucosa permeability, preventing apoptosis of damaged colonic cells and balancing Th1 and Th2 activity. Therefore, MSC-derived MP have high therapeutic potential for treating IBD, overcoming the deficiencies of living MSC therapy, and opening novel frontiers in inflammatory diseases medicine.