Ishioka Shigeki, Hosokawa Takashi, Ikeda Taro, Konuma Noriyoshi, Kaneda Hide, Ohashi Kensuke, Furuya Takeshi, Masuko Takayuki, Taniguchi Hiroaki, Kano Koichiro, Koshinaga Tsugumichi, Matsumoto Taro
Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo, 173-8610, Japan.
Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama, 330-8503, Japan.
Pediatr Surg Int. 2020 Jul;36(7):799-807. doi: 10.1007/s00383-020-04681-5. Epub 2020 May 24.
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.
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, CD4CD45RB T cells were intraperitoneally injected into SCID mice. One week later, DFAT cells (1 × 10, 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.
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.
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.
我们之前的研究表明，成熟脂肪细胞来源的去分化脂肪（DFAT）细胞具有与间充质干细胞相似的多能性。在此，我们检测了DFAT细胞在体外的免疫调节潜力以及DFAT细胞移植在小鼠炎症性肠病（IBD）模型中的治疗效果。
评估DFAT细胞共培养对T细胞增殖的影响以及DFAT细胞中免疫抑制相关基因的表达。为了建立IBD模型，将CD4CD45RB T细胞腹腔注射到SCID小鼠体内。一周后，腹腔注射DFAT细胞（1×10，DFAT组）或生理盐水（对照组）。随后每周测量体重，并在给予T细胞后5周评估IBD的临床和组织学评分。
共培养的DFAT细胞以细胞密度依赖性方式抑制T细胞增殖。TNFα刺激使DFAT细胞中TRAIL、IDO1和NOS2的基因表达上调。与对照组相比，DFAT组改善了IBD相关的体重减轻、IBD临床和组织学评分。
DFAT细胞具有免疫调节潜力，细胞移植促进了IBD模型中结肠损伤的恢复并改善了临床症状。DFAT细胞可能在IBD的治疗中发挥重要作用。
