Mesenchymal stem/stromal cells from gingival papilla: a novel tool for odontostomatological regenerative medicine

OBJECTIVES In dentistry, the use of oral and dental stem cells has become an attractive approach for the regeneration of tooth and periodontal tissues.In particular, oral soft tissues represent a convenient source of Mesenchymal Stem/Stromal cells (MSCs) owing to the minimal invasive withdrawal procedures. In the oral environment, gingival tissue represents the first important barrier against external offensive insults (e.g. chemicals, viruses and bacteria) and its peculiar properties allow a rapid wound-healing in the absence of scarring. Herein, MSCs isolated from gingival papilla (GinPa-MSCs) are proposed for odontostomatological regenerative medicine. MATERIALS AND METHODS: MSCs have been isolated from gingival papilla of donors undergoing oral surgery, after written consent. Primary cultures were characterized for their proliferation, clonogenicity (CFU-F assay), mesenchymal stem cell marker expression and multi-differentiative ability towards mesodermal lineages. In addition, GinPa-MSCs were analyzed by TEM and tested as possible vehicles for drug delivery. Statistical analysis was performed by Student's t test using GraphPadInStat program or by regression analysis using MicrosoftExcel software. Data are expressed as mean ± SD and a difference of p≤ 0.05 was considered statistically significant. RESULTS A typical fibroblast-like morphology and a high self-renewing ability (DT=50.4±16.1 hours) was present in all the GinPa-MSC populations, which also displayed a high clonogenic potential (~20% CFU-F) and expressed the typical mesenchymal immunophenotype (CD73+, CD90+, CD105+, CD45-). Interestingly, a mild positivity for CD14 (~32%) was found and further investigated by TEM analysis. GinPa-MSCs increased collagen production (+79%) and ECM deposition (+100%) when induced to differentiate towards osteogenic lineage, despite they displayed a high basal level of ALP activity. GinPa-MSCs possess a mild chondrogenic and adipogenic potential. In addition, when GinPa-MSCs were primed with the anticancer drug Paclitaxel (PTX), they were able to uptake and release the active molecule thus inhibiting the growth of CFPAC-1 carcinoma cells in vitro. DISCUSSION Our data indicate that GinPa-MSCs display peculiar characteristics that could be related to their unique function within the oral environment. The presence of a CD14+ monocyte-like subpopulation is most likely connected to gingival active defense mechanisms, as supported by the abundance of pinocytotic structures in their cytoplasm. GinPa MSC drug delivery properties are confirmed in vitro by the antitumor activity of their conditioned medium. CONCLUSIONS Taken together, our results suggest that gingival stromal cells represent an attractive candidate in maxillo-facial and dental regenerative medicine. Furthermore, their ability to uptake and release PTX represents an interesting perspective for drug delivery to treat cancer and other pathologies related to the odontostomatological apparatus.