2. Discovery, development and biological characteristic of GMSCs

Table 1 summarizes the advantages of GMSCs obtained from current studies in the

GMSC: Updates of Advances on Its Therapy in Immunological Diseases

3. Roles and mechanisms of GMSCs in treating immunological diseases

In response to the current challenges in the field of medicine on the efficacy and serious adverse effects of the current treatments, researchers are investigating the alternative therapies. In this regard, the use of MSCs represents a great promise for the treatment of a variety of immune-related diseases due to their potent properties of immunomodulatory ability [21, 22]. BMSCs and umbilical-cord MSCs (UC-MSCs) are widely studied because of their low immunogenicity [12, 23]. GMSCs, as a new subtype of MSCs, share strong abilities of immune regulation as MSCs from other tissues [24, 25]. As to update these advances of researches in GMSCs, we summarize the current recognition on the curative effects and mechanisms on

treatment of immunological diseases.

DOI: http://dx.doi.org/10.5772/intechopen.85153

immune and inflammation-related diseases (Table 2).

3.1 Immunoregulatory properties of GMSCs on autoimmune diseases

contacting or secreting molecules to modulate both innate and adaptive

Type 1 Diabetes Mellitus (T1DM) is an autoimmune disorder resulted from T cell-mediated destruction of pancreatic β-cells [32]. Hu et al. reported a clinical trial that implantation of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) from the umbilical cord for newly-onset T1DM restored the function of islet β-cells in a longer time by improving the level of HbA1c and C peptide without acute or chronic side effects, suggesting that the implantation of WJ-MSCs for the treatment of newly-onset T1DM is safe and effective [33]. Researches in experimental models of mice manifested that MSCs inhibited the expansion of Th1, Th17 cells and stimulated the proliferation of CD4+CD25+Foxp3+ T regulatory (Treg) cells by reducing the levels of pro-inflammatory cytokines such as TNF-α, IFN-γ, CCL2, IL-1β, IL-2 and IL-17 but increasing the expression of immunoregulatory cytokines such as IL-4, IL-10 and IL-13 [9]. Zhang et al. infused GMSCs to determine the therapeutic effect on T1DM model, just as other MSCs, showed that GMSCs administration, homing to pancreas lymph nodes and pancreas, could delay diabetes onset, ameliorate pathology in pancreas by regulating down IL-17 and IFN-γ of CD4+ and CD8+ T cell and induce the generation of induced regulatory T (iTreg) in vivo which may be regulated through CD39/CD73 signal pathway [34]. Treg cells are a crucial immune suppressor that maintains the immune tolerance and prevents

responses [31].

87

Autoimmune diseases are caused by defects in immune tolerance, resulting in that the body immune system failing to identify cells from their own or the foreign accompanied by the cellular or tissue damage [26]. Autoimmune diseases are categorized into systemic or organ-specific types according to the extent of tissue involvements [27]. The pathogenesis of autoimmune diseases is still not wellunderstood as multifactorial factors may be involved in at least both genetic and environmental factors [28, 29]. Although the conventional and biological therapies can somehow ameliorate clinical symptoms and decrease the morbidity and mortality, the limited efficiency, bone marrow toxicity and other side effects including infection and tumor are problematic [30]. Therefore it is desirable to find new strategies that can cure autoimmune diseases with minimal side effects. The MSCs therapy has been demonstrated to be likely as a new alternative approach. As a subset of MSCs, current studies show that GMSCs have even strong and better immunoregulatory effects than MSCs derived from other sources, through cell-cell

Gingiva is a unique oral tissue attached to the alveolar bone of tooth sockets, recognized as a biological mucosal barrier and a distinct component of oral mucosal immunity [14]. Wound healing within gingiva is characterized by rapid and fetallike scarless healing, contrary to the common scar formation in skin [15]. Gingival tissue is easily assessable and gingival cells can be easily isolated and expanded from patients or healthy donors. Gingival fibroblast-like cells, including fibrocytes, myofibroblasts, pericytes and mesenchymal stem cells, a heterogeneous group of cells with distinct properties and functions, were named gingival fibroblasts before 2009, playing key roles in tissue development, maintenance and repair, as well as contributing to various pathologies [16]. Zhang et al. was the first to isolate and characterize a new population of precursor cells from human gingival tissues, termed GMSCs, which exhibit three unique stem cell-like properties as MSCs derived from bone marrow and other postnatal tissues [17]. Based on the minimal characterization criteria for human MSCs of the International Society for Cellular Therapy [18], the population of GMSCs shows: (1) in vitro proliferation as plasticadherent cells with fibroblast-like morphology, colony-forming ability, (2) multipotent differentiation into different cell lineages, (3) positive expression of MSCs surface markers and stem cell-specific genes, negative of hemopoietic stem cell ones. Moreover, some studies reported that GMSCs manifested a higher expansion and telomerase activity and kept the features of MSCs, morphology and normal karyotype stable during cell expansion [19]. Recently, Gugliandolo et al. reported that most oncogenes of GMSCs at higher passengers were turned off, suggesting that long-term cultured GMSCs may be safer in the clinical setting [20].


#### Table 1.

Advantages of GMSCs in the treatment of immunological diseases compared to other MSCs according to the updated studies.

Table 1 summarizes the advantages of GMSCs obtained from current studies in the treatment of immunological diseases.
