Human Adipose Tissue-Derived Mesenchymal Stem Cells Induce Explosive T-Cell Proliferation
Human Adipose Tissue-Derived Mesenchymal Stem Cells Induce Explosive T-Cell Proliferation
复制标题
DOI：
10.1089/scd.2009.0368
复制
发表时间：
2010-12-01
影响因子：
4
通讯作者：
Hoogduijn, Martin J.
中科院分区：
文献类型：
--
作者：
Crop, Meindert J.;Baan, Carla C.;Hoogduijn, Martin J.
间充质干细胞（MSC）抑制同种异体激活的淋巴细胞的增殖。这种作用主要依赖于MSC分泌抗炎因子，并在炎症条件下增强。然而，MSC也产生可以潜在地激活静息免疫细胞的因子。充分了解MSC在炎症和非炎症条件下的行为是至关重要的，当考虑MSC的临床应用。将人脂肪组织来源的MSC与未活化的外周血单个核细胞（PBMC）一起培养，并检查PBMC的活化、增殖和功能。与自体或同种异体MSC共培养7天显著增加了PBMC的增殖（3倍）。在直接和transwell共培养系统中均观察到这种效应。与PBMC共培养的MSC显示促炎介质白细胞介素-6（IL-6）、IL-8、肿瘤坏死因子-α、生长因子碱性成纤维细胞生长因子和血管内皮生长因子-α以及抗炎因子吲哚胺2，3-双加氧酶的mRNA表达增加。去除MSC后，PBMC显示出惊人的进一步增殖增加，7天后最多为25倍。当PBMC保持在MSC存在下时，未观察到这种增殖增加。PBMC的增殖部分主要由具有高CD 25表达的CD 4（+）T细胞组成，并且CD 127（neg）FoxP 3（+）调节性T细胞的比例从总CD 4（+）T细胞的5.0%显著增加至8.5%。扩增的T细胞表现出对有丝分裂原或同种异体抗原刺激的正常反应。这些细胞的CD 25（阳性）部分具有免疫抑制能力。总之，MSC可以刺激静息T细胞的活化和增殖，并产生调节性T细胞。这些发现对于MSCs的临床应用具有重要意义。
Mesenchymal stem cells (MSCs) inhibit the proliferation of allo-activated lymphocytes. This effect is primarily dependent on the secretion of anti-inflammatory factors by MSCs and is enhanced under inflammatory conditions. MSCs, however, also produce factors that can potentially activate resting immune cells. Full understanding of the behavior of MSCs under inflammatory and noninflammatory conditions is crucial when clinical application of MSCs is considered. Human adipose tissue-derived MSCs were cultured with nonactivated peripheral blood mononuclear cells (PBMCs) and the activation, proliferation, and function of PBMCs were examined. Seven days of coculture with autologous or allogeneic MSCs significantly increased the proliferation of PBMCs (3-fold). This effect was observed in both direct and transwell coculture systems. MSCs cocultured with PBMCs showed increased mRNA expression of the proinflammatory mediators interleukin-6 (IL-6), IL-8, tumor necrosis factor-a, the growth factors basic fibroblast growth factor and vascular endothelial growth factor-alpha, and the anti-inflammatory factor indoleamine 2,3-dioxygenase. After removal of MSCs, PBMCs showed a spectacular further increase in proliferation, with a maximum of 25-fold after 7 days. This increase in proliferation was not seen when PBMCs were kept in the presence of MSCs. The proliferating fraction of PBMCs largely consisted of CD4(+) T-cells with high CD25 expression and the proportion of CD127(neg)FoxP3(+) regulatory T-cells significantly increased from 5.0% to 8.5% of total CD4(+) T-cells. The expanded T-cells demonstrated normal responses to mitogen or alloantigen stimulation. The CD25(positive) fraction of these cells had immunosuppressive capacity. In conclusion, MSCs can stimulate the activation and proliferation of resting T-cells and generate regulatory T-cells. These findings are important when MSCs are applied in the clinic.