Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan.
Transplantation. 2012 Jul 27;94(2):132-8. doi: 10.1097/TP.0b013e31825940a4.
Although human embryonic stem cells (ESCs) and mesenchymal stem cells (MSCs) from various sources display immunomodulatory effects, direct comparisons among these classes of stem cells have not been reported.
Peripheral blood mononuclear cell suppression assays and carboxyfluorescein diacetate succinimidyl ester assays were used to assess the immunosuppressive effects of stem cells. Gene expression was measured using DNA microarrays. Enzyme-linked immunosorbent assays were used to determine interleukin (IL)-6 levels.
We found that fetal-type MSCs proliferated significantly faster than adult-type MSCs. Compared with ESCs grown on feeder cells, ESCs grown in feeder cell-free conditions exhibited decreased immunosuppressive effects. The suppressive effects of ESCs were significantly stronger than those of MSCs, and the suppressive effects of fetal-type MSCs were significantly stronger than those of adult-type MSCs at each tested dose level. Analysis of gene expression by microarray and MetaCore pathway mapping revealed changes in eight different immune response pathways; we observed that IL-6 gene expression was highly significantly involved in all eight pathways. Significantly higher IL-6 elevation ratios (IL-6after:IL-6before) were found in ESCs compared with fetal-type MSCs, and these were also found in fetal-type MSCs compared with adult-type MSCs. Furthermore, IL-6 levels were found to correlate with cell dosages of MSCs and the suppressive effects.
The ease of obtaining fetal-type MSCs and their rapid proliferation make these cells ideal candidates for cell-based therapies, especially for diseases associated with immune responses, given the immunosuppressive effects of these cells. IL-6 might play an important role in the immunosuppressive effects of various stem cells.
尽管来自不同来源的人类胚胎干细胞（ESCs）和间充质干细胞（MSCs）均具有免疫调节作用，但尚未对这些类别的干细胞进行直接比较。
使用外周血单个核细胞抑制试验和羧基荧光素二乙酸琥珀酰亚胺酯试验来评估干细胞的免疫抑制作用。使用 DNA 微阵列测量基因表达。酶联免疫吸附试验用于测定白细胞介素（IL）-6 水平。
我们发现胎儿型 MSC 比成人型 MSC 增殖速度明显更快。与在饲养细胞上生长的 ESCs 相比，在无饲养细胞条件下生长的 ESCs 表现出降低的免疫抑制作用。与 MSC 相比，ESC 的抑制作用明显更强，在每个测试剂量水平下，胎儿型 MSC 的抑制作用均明显强于成人型 MSC。通过微阵列和 MetaCore 途径映射进行的基因表达分析揭示了八种不同免疫反应途径的变化；我们观察到 IL-6 基因表达高度参与了所有八个途径。与胎儿型 MSC 相比，在 ESCs 中发现了更高的 IL-6 升高比率（IL-6 后：IL-6 前），并且在胎儿型 MSC 中也发现了更高的 IL-6 升高比率（IL-6 后：IL-6 前），与成人型 MSC 相比。此外，还发现 IL-6 水平与 MSC 的细胞剂量和抑制作用相关。
胎儿型 MSC 易于获得且增殖迅速，使其成为细胞治疗的理想候选物，尤其是对于与免疫反应相关的疾病，因为这些细胞具有免疫抑制作用。IL-6 可能在各种干细胞的免疫抑制作用中发挥重要作用。
