TY - JOUR
T1 - Mesenchymal stromal cell-derived membrane particles
T2 - A novel cell-free therapy for inflammatory bowel diseases
AU - Serafini, Michele Aramburu
AU - Sirena, Dienifer Hermann
AU - da Silveira, Ana Beatriz Tittoni
AU - Franco-da-Silva, Monique
AU - Aubin, Mariana Rauback
AU - Garcez, Tuane Nerissa Alves
AU - Araújo, Anelise
AU - dos Santos Pereira, Fernanda
AU - Hoogduijn, Martin J.
AU - da Costa Gonçalves, Fabiany
AU - Paz, Ana Helena
N1 - Publisher Copyright: © 2023 Elsevier B.V.
PY - 2023/5
Y1 - 2023/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85151694892&partnerID=8YFLogxK
U2 - 10.1016/j.intimp.2023.110076
DO - 10.1016/j.intimp.2023.110076
M3 - Article
C2 - 37030123
AN - SCOPUS:85151694892
SN - 1567-5769
VL - 118
JO - International Immunopharmacology
JF - International Immunopharmacology
M1 - 110076
ER -