Immunosuppressive mechanisms of embryonic stem cells and mesenchymal stem cells in alloimmune response

Han, Kyu Hyun; Ro, Han; Hong, Ju Ho; Lee, Eun Mi; Cho, Bumrae; Yeom, Hye Jung; Kim, Myung Gyu; Oh, Kook Hwan; Ahn, Curie; Yang, Jaeseok

doi:10.1016/j.trim.2011.05.004

Cited by 51 publications

(37 citation statements)

References 38 publications

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“…These results point to the ability of SVF cells to play an effector role similar to that of both ASCs and BMSCs, which would occur during the early inflammatory phase of disease, supporting the possibility that uncultured SVF cells could also affect the generation of encephalitogenic effector T cells. Although BMSCs have been shown to reduce levels of IFNγ by direct contact, it is unclear whether ASCs and SVF cells utilize the same mechanism [56]. Although the mechanisms mediating such effects are still only partially understood, it is likely that they involve both direct cell-to-cell contact and paracrine signaling through soluble factors.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, IL-12 was reduced in the BMSC-treated group and further reduced in the SVF-treated group. Although this is the first study to show that SVF treatment reduced the levels of IL-12, BMSCs have been shown to reduce levels of IL-12 in a chronic EAE model [56,57]. Interestingly, murine BMSCs were shown to exert opposing effects on Th1 cells depending on the time of disease onset and the level of effector T-cell activation, suppressing all T cells when administered early during T-cell activation and able to decrease IFNγ and increase IL-17 once T cells become activated [58].…”

Section: Discussionmentioning

confidence: 99%

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Comparison of human adult stem cells from adipose tissue and bone marrow in the treatment of experimental autoimmune encephalomyelitis

et al. 2014

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IntroductionWhile administration of ex vivo culture-expanded stem cells has been used to study immunosuppressive mechanisms in multiple models of autoimmune diseases, less is known about the uncultured, nonexpanded stromal vascular fraction (SVF)-based therapy. The SVF is composed of a heterogeneous population of cells and has been used clinically to treat acute and chronic diseases, alleviating symptoms in a range of tissues and organs.MethodsIn this study, the ability of human SVF cells was compared with culture-expanded adipose stem cells (ASCs) and bone-derived marrow stromal cells (BMSCs) as a treatment of myelin oligodendrocyte glycoprotein (35–55)-induced experimental autoimmune encephalitis in C57Bl/6J mice, a well-studied multiple sclerosis model (MS). A total of 1 × 106 BMSCs, ASCs, or SVF cells were administered intraperitoneally concomitantly with the induction of disease. Mice were monitored daily for clinical signs of disease by three independent, blinded investigators and rated on a scale of 0 to 5. Spinal cords were obtained after euthanasia at day 30 and processed for histological staining using luxol fast blue, toluidine blue, and hematoxylin and eosin to measure myelin and infiltrating immune cells. Blood was collected from mice at day 30 and analyzed by enzyme-linked immunosorbent assay to measure serum levels of inflammatory cytokines.ResultsThe data indicate that intraperitoneal administration of all cell types significantly ameliorates the severity of disease. Furthermore, the data also demonstrate, for the first time, that the SVF was as effective as the more commonly cultured BMSCs and ASCs in an MS model. All cell therapies also demonstrated a similar reduction in tissue damage, inflammatory infiltrates, and sera levels of IFNγ and IL-12. While IFNγ levels were reduced to comparable levels between treatment groups, levels of IL-12 were significantly lower in SVF-treated than BMSC-treated or ASC-treated mice.ConclusionsBased on these data, it is evident that SVF cells have relevant therapeutic potential in an animal model of chronic MS and might represent a valuable tool for stem cell-based therapy in chronic inflammatory disease of the central nervous system. SVF offers advantages of direct and rapid isolation procedure in a xenobiotic-free environment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comparison of human adult stem cells from adipose tissue and bone marrow in the treatment of experimental autoimmune encephalomyelitis

et al. 2014

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“…For example, MSCs possess self-renewal capacity, multilineage differentiation potential and lack co-stimulatory factors, such as CD80, CD86 and human leukocyte antigen (HLA); thus, they fail to activate allo-or xenogeneic immune cells due to the lack of immunogenicity (1)(2)(3). MSCs also have an immunosuppressive ability as they can inhibit the proliferation and function of T cells, B cells, natural killer (NK) cells and antigen-presenting cells (4).…”

Section: Introductionmentioning

confidence: 99%

The role of Toll-like receptor 3 and 4 in regulating the function of mesenchymal stem cells isolated from umbilical cord

Zhang

Liu

et al. 2015

International Journal of Molecular Medicine

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Abstract. Mesenchymal stem cells (MSCs) have been applied to cell-based therapy due to their multiple differentiation ability, the low expression of co-stimulatory molecules and immunosuppressive properties. Despite their immunomodulatory role, the issue of the survival and permanence of MSCs at the site of injury has not yet been fully resolved. Therefore, in order to improve the therapeutic potential of MSCs, it is important to study the mechanisms mediating the relative instability of MSCs in clinical trials. The Toll-like receptors (TLRs) are an important component of innate and adaptive immune responses. In this study, we demonstrate that the activation of two TLRs, namely TLR3 and TLR4, in human umbilical cord-derived MSCs (UCMSCs) induces the expression of inflammatory markers. In addition, as shown by our results, TLR3 upregulated the expression of stem cell markers, while TLR4 downregulated their expression. The upregulation in the expression of the inflammatory markers did not alter the immune status of the UCMSCs or mediate the immune attack of the MSCs by allogeneic immune cells. We found that the activation of TLR3 inhibited the differentiation of UCMSCs into osteocytes, while that of TLR4 increased this differentiation to a certain extent. Taken together, the results of this study provide a new role for TLR3 and TLR4 as regulators of the biological functions of UCMSCs.

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“…Resent data suggest that the balance of Th17/Tregs contributes to the MSC-mediated immunosuppressive effects [32]. They prove that MSCs suppress the survival as well as the proliferation of T cells partially by increasing the proportion of regulatory T cells in vitro [33]. What is more, MSCs can negatively regulate both Th1 and Th17 responses and restore the balance of Th17/ Tregs in experimental autoimmune uveoretinitis [34].…”

Section: Discussionmentioning

confidence: 99%

Gene delivery with IFN-γ-expression plasmids enhances the therapeutic effects of MSCs on DSS-induced mouse colitis

et al. 2015

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Immunosuppressive mechanisms of embryonic stem cells and mesenchymal stem cells in alloimmune response

Cited by 51 publications

References 38 publications

Comparison of human adult stem cells from adipose tissue and bone marrow in the treatment of experimental autoimmune encephalomyelitis

Comparison of human adult stem cells from adipose tissue and bone marrow in the treatment of experimental autoimmune encephalomyelitis

The role of Toll-like receptor 3 and 4 in regulating the function of mesenchymal stem cells isolated from umbilical cord

Gene delivery with IFN-γ-expression plasmids enhances the therapeutic effects of MSCs on DSS-induced mouse colitis

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