Characterization of mesenchymal stem cells from human normal and hyperplastic gingiva

Abstract

Human gingiva plays an important role in the maintenance of oral health and shows unique fetal-like scarless healing process after wounding. Here we isolate and characterize mesenchymal stem cells from human normal and hyperplastic gingival tissues (N-GMSC and H-GMSC, respectively). Immunocytochemical staining indicated that gingival lamina propria contained Stro-1 and SSEA-4 positive cells, implying existence of putative gingival MSC. Under attachment-based isolating and culturing condition, gingival MSC displayed highly clonogenic and long-term proliferative capability. By using single colony isolation and expansion approaches, we found both N-GMSC and H-GMSC possessed self-renewal and multipotent differentiation properties. N-GMSC and H-GMSC showed distinct immunoregulatory functions in a murine skin allograft setting via up-regulation of putative systemic regulatory T cells (Tregs). N-GMSC and H-GMSC were capable of regenerating collagenous tissue following in vivo transplantation, in which H-GMSC exhibited more robust regenerative capability. These findings suggest that gingival tissue contains tissue-specific mesenchymal stem cell population and is an ideal resource for immunoregulatory therapy due to its substantial availability and accessibility. In addition, gingival MSC over-activation may contribute to gingival hyperplastic phenotype.

Human exfoliated deciduous teeth and oral mucosa: promising applications in tissue regeneration

“…peroxisome proliferator-activated receptor γ) and chondrogenic markers (i.e. collagen 2A1 and aggrecan) [41][42][43][44] .…”

Cell Surface Sialylated N-Glycan Alterations during Development

“…Human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) are valuable resources for cell replacement therapies. Determination of specific markers are required for effective utilization of stem cells and elimination of tumor initiating cells (57). For this purpose, cell surface glycan variations have been investigated to detect the most appropriate markers.…”

Human Oral Mucosa and Gingiva

“…These biological properties suggest that MSCs derived from gingiva might possess some intrinsic properties distinct from those of oral mucosa-derived MSCs (Tang et al, 2011). Recent studies have shown that a population of clustered cells in the lamina propria layer of human gingiva displays positive signals for pluripotency-related markers, Oct-4, SSEA-4, and Stro-1 (Zhang et al, 2009;Tang et al, 2011), with some co-expressing Oct-4/SSEA-4 or Oct4/Stro-1 (Zhang et al, 2009). Additionally, the human oral mucosal/gingival lamina propria (OMLP) has been shown to harbor a population of cells positive for lowaffinity neurotrophin (p75), a marker of neural stem cells, organized in cord-like structures that are also positively stained for Oct-4 and Sox2 (Marynka-Kalmani et al, 2010).…”

“…Importantly, human oral mucosa-and gingiva-derived MSCs invariably display a higher proliferation rate than do BMSCs (Zhang et al, 2009;Davies et al, 2010;Marynka-Kalmani et al, 2010;Tomar et al, 2010;Tang et al, 2011), which was likely attributed to the constitutive expression of human reverse telomerase transcriptase (hTERT) (Zhang et al, 2009;Davies et al, 2010). Moreover, the in vivo self-renewal capacity of gingiva-derived MSCs has been demonstrated by serial subcutaneous (s.c.) transplantation in immunocompromised mice (Zhang et al, 2009;Tang et al, 2011). These findings support that a population of MSCs with potent self-renewal and proliferative potentials can be readily isolated from human oral mucosa and gingival tissues and reliably expanded ex vivo for large-scale culture.…”

“…Like BMSCs and ADSCs, human oral mucosa-/gingiva-derived MSCs can also differentiate into osteoblasts, adipocytes, and chondrocytes under specific in vitro differentiating conditions (Zhang et al, 2009;Davies et al, 2010;Fournier et al, 2010;Marynka-Kalmani et al, 2010;Mitrano et al, 2010;Tomar et al, 2010;Tang et al, 2011;Wang et al, 2011). In addition to these tri-lineage potentials, oral mucosa-/gingiva-derived MSCs are capable of differentiating into endodermal and ectodermal lineages, including various types of neural cells (Zhang et al, 2009;Davies et al, 2010;Marynka-Kalmani et al, 2010).…”