5. Conclusion

Fas/FasL in GMSCs coupling-induced T cells migration and T-cell apoptosis to

Atherosclerosis is the major cause of cardiovascular diseases. Current evidences indicate that inflammation is involved in the pathogenesis of atherosclerosis and monocytes/macrophages are the major inflammatory cells [50]. Zhang et al. firstly indicated that GMSCs decreased inflammatory level, plaque size and lipid deposition in mice model in vivo, partly by inhibiting macrophage foam cell formation, suppressing the activation of M1 macrophages and promoting their development

Periodontitis is a widespread bacterially induced immune-inflammatory disorder of the periodontium, featured with a progressive destruction of the tooth-supporting structures [52]. The milieu of bacterial biofilms challenges and activates host innate

chemokines for inflammatory cells recruitment, striking the balance of osteoblast and osteoclast [53]. MSCs from bone marrow, adipose, dental pulp and periodontal ligament have been testified to, in vivo, newly form periodontal bones, collagen fibers, periodontal ligament-like tissue and cementoid tissue indicating periodontium regeneration [54]. GMSCs also were proved to generate new cementum-like tissue,

Murine contact hypersensitivity (CHS) as a model similar to human allergic contact is caused by delayed-type hypersensitivity responses to antigens that come into contact with the skin [57]. The pathological process consists of sensitization phase, the elicitation or challenge phase, and resolution/regulation phase [58]. In this process, allergen-specific effector T cells and various types of innate immune cells are involved [59]. In 2011, Su et al. investigated the immunoregulatory role of GMSCs and for first time found that i.v. injection of GMSC significantly attenuated the CHS appearance at different phases of CHS, and showed that GMSCs-derived PGE2 played a crucial role in their inhibitory effect on dendritic cells and mast cells [60]. Li et al. further testified that PGE2–EP3 signaling played an important role in

Cutaneous wound healing involves in three phases: inflammation, tissue formation, and remodeling [62]. Studies have demonstrated that systemically injected MSCs can home to injury sites accelerating wound repair [63]. Because of the rapid and fetal-like healing of gingival trauma, researchers have focused on the effect and mechanism of GMSCs. Experiments in vitro suggested that GMSCs were capable of switching macrophages from classical activation or proinflammatory M1 phenotype to an anti-inflammatory profile of M2 macrophages by soluble factors such IL-6, COX-2 and GM-CSF [64]. In vivo mice model suggested that enhancement of wound healing by systemic infusion of GMSCs related to enhanced reepithelialization, collagen deposition and angiogenesis [64]. Compared with BMSCs, Linard et al. reported that gingival fibroblasts (GFs) intradermally injected in irradiated skin induced earlier development of thick, fully regenerated epidermis, skin appendages and hair follicles [65]. GFs also modified expression of ECMrelated gene, ECM components (tenascin-C and a-smooth muscle actin) and wound healing-related factors, like TGF-β1 and CTGF [65]. While the influence to macrophage recruitment and differentiation of GFs was in accordance with Zhang et al., other studies presented that GMSC-derived exosomes accelerated wound healing in

and adoptive immune systems to produce pro-inflammatory cytokines and

bone and sharpey fibers in dog and pig model of periodontitis [55, 56].

3.4 The contribution of GMSCs to contact hypersensitivity

the immunomodulatory functions of GMSCs in murine CHS [61].

3.5 Wound healing

90

maintain immunomodulation of GMSCs in vivo and in vitro [49].

into the M2 phenotype via IDO and CD73 signals [51].

Update on Mesenchymal and Induced Pluripotent Stem Cells

The existing studies have documented that GMSCs have self-renewal, multi-lineage differentiation potential, and immunomodulatory properties. These properties make GMSCs an alternative cell-based therapy of autoimmune and inflammation-related diseases. Plenty of internal and external factors may affect their functions of renewal, regeneration and immunoregulation. Moreover, the specific mechanisms and clinical efficacies are indistinct. Future studies and clinical trials should be implemented to elaborate mechanisms and therapeutic effects of immunomodulatory properties in detail on various inflammatory and immunological diseases.

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