title: The comparison of interleukin 6-associated immunosuppressive effects of human ESCs, fetal-type MSCs, and adult-type MSCs.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan.
authors: Chin-Kan
authors: CK
authors: Chan
authors: Kang-Hsi
authors: KH
authors: Wu
authors: Yun-Shen
authors: YS
authors: Lee
authors: Shiaw-Min
authors: SM
authors: Hwang
authors: Maw-Sheng
authors: MS
authors: Lee
authors: Shuen-Kuei
authors: SK
authors: Liao
authors: En-Hui
authors: EH
authors: Cheng
authors: Lai-Chu
authors: LC
authors: See
authors: Chi-Neu
authors: CN
authors: Tsai
authors: Ming-Ling
authors: ML
authors: Kuo
authors: Jing-Long
authors: JL
authors: Huang
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000502:physiology*; D020869:Gene Expression Profiling; D006801:Humans; D007108:Immune Tolerance; D015850:Interleukin-6 / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000502:physiology*
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6