Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Stem Cells Transl Med. 2013 Jun;2(6):455-63. doi: 10.5966/sctm.2012-0184. Epub 2013 May 21.
Adipose tissue-derived multipotent stromal cells (AT-MSCs) are studied as an alternative to bone marrow-derived multipotent stromal cells (BM-MSCs) for immunomodulatory treatment. In this study, we systematically compared the immunomodulatory capacities of BM-MSCs and AT-MSCs derived from age-matched donors. We found that BM-MSCs and AT-MSCs share a similar immunophenotype and capacity for in vitro multilineage differentiation. BM-MSCs and AT-MSCs showed comparable immunomodulatory effects as they were both able to suppress proliferation of stimulated peripheral blood mononuclear cells and to inhibit differentiation of monocyte-derived immature dendritic cells. However, at equal cell numbers, the AT-MSCs showed more potent immunomodulatory effects in both assays as compared with BM-MSCs. Moreover, AT-MSCs showed a higher level of secretion of cytokines that have been implicated in the immunomodulatory modes of action of multipotent stromal cells, such as interleukin-6 and transforming growth factor-β1. This is correlated with higher metabolic activity of AT-MSCs compared with BM-MSCs. We conclude that the immunomodulatory capacities of BM-MSCs and AT-MSCs are similar, but that differences in cytokine secretion cause AT-MSCs to have more potent immunomodulatory effects than BM-MSCs. Therefore, lower numbers of AT-MSCs evoke the same level of immunomodulation. These data indicate that AT-MSCs can be considered as a good alternative to BM-MSCs for immunomodulatory therapy.
脂肪组织来源的多能基质细胞(AT-MSCs)被研究为替代骨髓来源的多能基质细胞(BM-MSCs)用于免疫调节治疗。在这项研究中,我们系统地比较了来自年龄匹配供体的 BM-MSCs 和 AT-MSCs 的免疫调节能力。我们发现 BM-MSCs 和 AT-MSCs 具有相似的免疫表型和体外多谱系分化能力。BM-MSCs 和 AT-MSCs 表现出相似的免疫调节作用,因为它们都能够抑制刺激的外周血单个核细胞的增殖,并抑制单核细胞衍生的未成熟树突状细胞的分化。然而,在相同的细胞数量下,与 BM-MSCs 相比,AT-MSCs 在这两种测定中显示出更强的免疫调节作用。此外,AT-MSCs 表现出更高水平的细胞因子分泌,这些细胞因子与多能基质细胞的免疫调节作用模式有关,如白细胞介素 6 和转化生长因子-β1。这与 AT-MSCs 与 BM-MSCs 相比具有更高的代谢活性相关。我们得出结论,BM-MSCs 和 AT-MSCs 的免疫调节能力相似,但细胞因子分泌的差异导致 AT-MSCs 具有比 BM-MSCs 更强的免疫调节作用。因此,较少数量的 AT-MSCs 可以引发相同水平的免疫调节。这些数据表明,AT-MSCs 可以被认为是 BM-MSCs 用于免疫调节治疗的良好替代品。