Therapeutic potential of mature adipocyte-derived dedifferentiated fat cells for inflammatory bowel disease

Author:

Ishioka Shigeki,Hosokawa Takashi,Ikeda Taro,Konuma Noriyoshi,Kaneda Hide,Ohashi Kensuke,Furuya Takeshi,Masuko Takayuki,Taniguchi Hiroaki,Kano Koichiro,Koshinaga Tsugumichi,Matsumoto TaroORCID

Abstract

Abstract Purpose Our 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. Methods The 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. Results The 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. Conclusion DFAT 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.

Funder

JSPS KAKENHI

Nihon University President Grant Initiative

Ministry of Education, Culture, Sports, Science and Technology

Publisher

Springer Science and Business Media LLC

Subject

General Medicine,Surgery,Pediatrics, Perinatology and Child Health

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