Abstract
PurposeOur previous studies demonstrated that mature adipocyte-derived dedifferentiated fat (DFAT) cells possess similar multipotency as mesenchymal stem cells. Here, we examined the immunoregulatory potential of DFAT cells in vitro and the therapeutic effect of DFAT cell transplantation in a mouse inflammatory bowel disease (IBD) model.MethodsThe effect of DFAT cell co-culture on T cell proliferation and expression of immunosuppression-related genes in DFAT cells were evaluated. To create IBD, CD4+CD45RBhigh T cells were intraperitoneally injected into SCID mice. One week later, DFAT cells (1 × 105, DFAT group) or saline (Control group) were intraperitoneally injected. Subsequently bodyweight was measured every week and IBD clinical and histological scores were evaluated at 5 weeks after T cell administration.ResultsThe T cell proliferation was inhibited by co-cultured DFAT cells in a cell density-dependent manner. Gene expression of TRAIL, IDO1, and NOS2 in DFAT cells was upregulated by TNFα stimulation. DFAT group improved IBD-associated weight loss, IBD clinical and histological scores compared to Control group.ConclusionDFAT cells possess immunoregulatory potential and the cell transplantation promoted recovery from colon damage and improved clinical symptoms in the IBD model. DFAT cells could play an important role in the treatment of IBD.
Highlights
Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is a family of chronic, idiopathic, and relapsing diseases characterized by dysfunction of mucosal T cells and altered cellular inflammation that lead to damage of the distal small intestine and colonic mucosa [1]
Induction of colitis by adoptive transfer of CD4+CD45RBhigh T cells into severe combined immunodeficiency (SCID) mice was performed essentially as described previously [23]. CD4+CD45RBhigh T cells (3 × 105 cells in 200 μl phosphate-buffered saline (PBS)) isolated from a BALB/c mouse spleen were intraperitoneally injected into SCID mice (n = 12)
The mice were sacrificed at 5 weeks after T cell administration, and after immobilization with 4% paraformaldehyde, the colon was taken and the IBD clinical score [24] was evaluated in each group
Summary
Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is a family of chronic, idiopathic, and relapsing diseases characterized by dysfunction of mucosal T cells and altered cellular inflammation that lead to damage of the distal small intestine and colonic mucosa [1]. The widely accepted hypothesis for the etiology of IBD is that of a disturbed interaction between the host immune system and the commensal microflora and other luminal antigens. This interaction, in turn, leads to ongoing mucosal inflammation [3]. MSCs were shown to modulate both the innate and adaptive immune systems [7,8,9,10]. These cells may inhibit the function of various immune cells, including dendritic cells, T cells, B cells, and natural killer cells.
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