Gingival Mesenchymal Stem/Progenitor Cells: A Unique Tissue Engineering Gem

Abstract

The human gingiva, characterized by its outstanding scarless wound healing properties, is a unique tissue and a pivotal component of the periodontal apparatus, investing and surrounding the teeth in their sockets in the alveolar bone. In the last years gingival mesenchymal stem/progenitor cells (G-MSCs), with promising regenerative and immunomodulatory properties, have been isolated and characterized from the gingival lamina propria. These cells, in contrast to other mesenchymal stem/progenitor cell sources, are abundant, readily accessible, and easily obtainable via minimally invasive cell isolation techniques. The present review summarizes the current scientific evidence on G-MSCs' isolation, their characterization, the investigated subpopulations, the generated induced pluripotent stem cells- (iPSC-) like G-MSCs, their regenerative properties, and current approaches for G-MSCs' delivery. The review further demonstrates their immunomodulatory properties, the transplantation preconditioning attempts via multiple biomolecules to enhance their attributes, and the experimental therapeutic applications conducted to treat multiple diseases in experimental animal models in vivo. G-MSCs show remarkable tissue reparative/regenerative potential, noteworthy immunomodulatory properties, and primary experimental therapeutic applications of G-MSCs are very promising, pointing at future biologically based therapeutic techniques, being potentially superior to conventional clinical treatment modalities.

Figure 1

Schematic drawing of the oral tissues contributing to the developmental origin of human gingival lamina propria. DFSCs: dental follicle stem cells, G-MSCs: gingival mesenchymal stem/progenitor cells, PDLSCs: periodontal ligament stem cells.

Figure 2

Sources of oral stem/progenitor cells isolated. DFSCs: dental follicle stem cells, G-MSCs: gingival mesenchymal stem/progenitor cells, PDLSCs: periodontal ligament stem cells, SHEDs: stem cells from the human exfoliated deciduous teeth, DPSCs: dental pulp stem cells, BM-MSCs: bone marrow mesenchymal stem cells, and SCAP: stem cells from the apical papilla.

Figure 3

Immunomodulatory “crosstalk” between G-MSCs and mast cells, macrophages (with their M1 and M2 phenotypes), dendritic cells, and T-cells. COX-2: cyclooxygenase-2; PGE₂: prostaglandin E₂; GM-CSF: granulocyte-macrophage colony-stimulating factor; INF: interferon; IL: interleukin; TGF: transforming growth factor; IDO: indoleamine 2,3-dioxygenase; LPS: lipopolysaccharide.