Pharmacological Retention of Oral Mucosa Progenitor/Stem Cells

Abstract

Oral mucosa progenitor/stem cells reside as a small-sized cell population that eventually differentiates concurrently with an increase in cell size. Activation of the mammalian target of rapamycin (mTOR) leads to an increase in cell size. We hypothesized that rapamycin, a specific inhibitor of mTOR, will maintain primary human oral keratinocytes as a small-sized, undifferentiated cell population capable of retaining their proliferative capacity. Primary, rapamycin-treated (2 nM, 20 nM) oral keratinocytes showed a diminished cell size that correlated with a higher clonogenicity, a longer-term proliferative potential, and a slower cycling cell population concurrent with decreased expression of a differentiation marker when compared with untreated cells. Only the 2-nM rapamycin-treated oral keratinocytes maintained their ability to regenerate oral mucosa in vitro after 15 weeks of culture. Rapamycin, a Food and Drug Administration-approved drug, may have applicability for use in creating a highly proliferative cell population for use in regenerative medicine.

Intraoral Grafting of Tissue-Engineered Human Oral Mucosa

“…Studies are presently underway in the authors’ lab employing physical and pharmacologic methodologies consistent with the GMP conditions to develop techniques that will lead the cultured primary oral keratinocytes to increase the progenitor/stem cell population; these studies will allow this technology to be brought into clinical use more easily for the development of a more robust EVPOME for intraoral grafting procedures. 30–31 …”

Dental and Craniofacial Tissue Stem Cells: Sources and Tissue Engineering Applications

“…GMSCs are reported in the gingival lamina propria which attaches directly to the periosteum of the underlying bone [ 21 ]. In addition, a neural crest stem cell-like population has also been isolated from the adult human gingival lamina propria which are termed oral mucosa stem cells (OMSCs) [ 22 ].…”

“…Stem cell populations which have been identifi ed and characterised within these tissues include dental pulp stem cells (DPSCs) [ 9 ], stem cells from the apical papilla (SCAPs) [ 10 -12 ], dental follicle precursor cells (DFSCs) [ 13 -16 ], periodontal ligament stem cells (PDLSCs) [ 17 , 18 ], stem cells from human exfoliated deciduous teeth (SHEDs) [ 19 ] and tooth germ progenitor cells (TGPCs) [ 20 ]. Furthermore, the presence of other, perhaps as yet less well characterised stem cell types within the orofacial region have been reported including oral epithelial progenitor/stem cells (OESCs) [ 21 ], gingiva-derived MSCs (GMSCs) [ 22 , 23 ], periosteum-derived stem cells (PSCs) [ 24 ] and salivary gland-derived stem cells (SGSCs) [ 25 -27 ]. In addition, well characterised MSCs which are not exclusive to the oral and craniofacial tissues, include bone marrowderived MSCs (BMMSCs) [ 28 ], which can be harvested from maxilla and mandibular bone, as well as adipose tissue-derived stem cells (ADSCs) [ 29 ].…”

Cellular Systems for Studying Human Oral Squamous Cell Carcinomas

“…Indeed, although most of our current knowledge on epithelial stem cell biology is based on the study of multipotent epithelial stem cells residing in the bulge region within the hair follicle, it is still not even clear whether these follicle stem cells do in fact contribute to the interfollicular epidermis under physiological situations, or whether multiple lineage restricted stem cell populations give rise to each histologically defined dermal structure, the epidermis, hair follicles, and sebaceous glands. This situation is expected to be much simpler for oral epithelial stem cells, which only need to proliferate and differentiate into stratified epithelia thus enabling to ask fundamental questions in the stem cell research field in a well-defined and biologically relevant system [22,25].…”

“…As described earlier in this chapter, new techniques of culturing oral epithelial cells now makes its possible in obtaining large cultures from small pieces of donor tissues, and affords an excellent opportunity to explore their biological properties in greater detail, and to translate this information potentially to the field of oral regenerative medicine [22,25]. However, before embarking on such an endeavor we must appreciate that monolayer cultures of cells are not accurate representations of tissue in vivo, primarily because they lack the types of interactions that cells have with other cells and with the extracellular matrix [40].…”