Adipose-Derived Stem Cells From Patients With Ulcerative Colitis Exhibit Impaired Immunosuppressive Function.
Adipose-Derived Stem Cells From Patients With Ulcerative Colitis Exhibit Impaired Immunosuppressive Function.
复制标题
来自溃疡性结肠炎患者的脂肪干细胞表现出免疫抑制功能受损
DOI：
10.3389/fcell.2022.822772
复制
发表时间：
2022
影响因子：
5.5
通讯作者：
Ma Z
中科院分区：
文献类型：
--
作者：
Wu X;Mu Y;Yao J;Lin F;Wu D;Ma Z
脂肪源性干细胞（ADSC）能够调节免疫反应，并用于治疗溃疡性结肠炎（UC）。然而，来自炎症或自身免疫性疾病患者的ADSC可能表现出免疫抑制缺陷。我们研究了来自UC患者的ADSC用于自体细胞治疗的用途，特别是来自健康供体（H-ADSC）和UC患者（P-ADSC）的ADSC在各种功能方面的用途，包括分化、增殖、分泌和免疫抑制。在急性或慢性结肠炎的小鼠模型中检查P-ADSC治疗UC的功效。H-ADSC和P-ADSC在细胞形态、大小、成脂分化能力和细胞表面标志物方面相似。我们发现P-ADSCs的增殖能力、克隆能力、成骨和软骨分化潜能均低于H-ADSCs。P-ADSCs抑制外周血单个核细胞增殖、抑制CD 25和CD 69标记物表达、减少炎症相关细胞因子干扰素-γ和肿瘤坏死因子-α的产生以及降低其对A549细胞的细胞毒性作用的能力减弱。当用炎性细胞因子致敏时，P-ADSC分泌较低水平的前列腺素E2、吲哚胺2，3-双加氧酶和肿瘤坏死因子-α-诱导蛋白6，这介导了它们降低的免疫效力。此外，P-ADSC表现出较弱的治疗效果比H-ADSC，确定疾病活动，组织学，髓过氧化物酶活性，和体重。这些发现表明ASC的免疫抑制特性受供体代谢特征的影响。这项研究首次表明，UC患者存在缺陷性ADSC免疫抑制，表明自体ADSC移植可能不适合UC患者。
Adipose-derived stem cells (ADSCs) are able to modulate the immune response and are used for treating ulcerative colitis (UC). However, it is possible that ADSCs from patients with inflammatory or autoimmune disorders may show defective immunosuppression. We investigated the use of ADSCs from UC patients for autologous cell treatment, specifically, ADSCs from healthy donors (H-ADSCs) and UC patients (P-ADSCs) in terms of various functions, including differentiation, proliferation, secretion, and immunosuppression. The efficacy of P-ADSCs for treating UC was examined in mouse models of acute or chronic colitis. Both H-ADSCs and P-ADSCs were similar in cell morphology, size, adipogenic differentiation capabilities, and cell surface markers. We found that P-ADSCs had lower proliferative capacity, cloning ability, and osteogenic and chondrogenic differentiation potential than H-ADSCs. P-ADSCs exhibited a diminished capacity to inhibit peripheral blood mononuclear cell proliferation, suppress CD25 and CD69 marker expression, decrease the production of inflammation-associated cytokines interferon-γ and tumor necrosis factor-α, and reduce their cytotoxic effect on A549 cells. When primed with inflammatory cytokines, P-ADSCs secreted lower levels of prostaglandin E2, indoleamine 2, 3-dioxygenase, and tumor necrosis factor-α–induced protein 6, which mediated their reduced immunopotency. Moreover, P-ADSCs exhibited weaker therapeutic effects than H-ADSCs, determined by disease activity, histology, myeloperoxidase activity, and body weight. These findings indicate that the immunosuppressive properties of ASCs are affected by donor metabolic characteristics. This study shows, for the first time, the presence of defective ADSC immunosuppression in UC, indicating that autologous transplantation of ADSCs may be inappropriate for patients with UC.
登录
查看更多内容
影响因子：
29.4
作者：
Howell KJ;Kraiczy J;Nayak KM;Gasparetto M;Ross A;Lee C;Mak TN;Koo BK;Kumar N;Lawley T;Sinha A;Rosenstiel P;Heuschkel R;Stegle O;Zilbauer M
通讯作者：
Zilbauer M
影响因子：
6
作者：
Kuca-Warnawin, Ewa;Skalska, Urszula;Kontny, Ewa
通讯作者：
Kontny, Ewa
影响因子：
6
作者：
Kuci, Zyrafete;Jordan, Christiane;Kuci, Selim
通讯作者：
Kuci, Selim
影响因子：
3.9
作者：
Hosseini-Asl SK;Mehrabani D;Karimi-Busheri F
通讯作者：
Karimi-Busheri F
影响因子：
4.5
作者：
Girdlestone, John;Pido-Lopez, Jeffrey;Navarrete, Cristina V.
通讯作者：
Navarrete, Cristina V.