Gingival papilla mesenchymal stromal cells and their potential role in clinical dentistry

Objective: In the last few years, great advances have been made in exploring the clinical potential of oral and dental stem cells. Indeed, in dentistry, the restoration of tooth and periodontal tissues is now focusing on the use of Mesenchymal Stromal Cells (MSCs) of oral origins, such as tooth pulp (DPSCs), periodontal ligament (PDLSCs), dental follicle (DFPCs) and apical papilla (SCAPs). In particular, thanks to the easy and minimally invasive withdrawal procedure, oral soft tissues represent a convenient source of MSCs. Gingival tissue is composed by a variety of cell types and in the oral environment it represents the first important barrier against external offensive insults (e.g. chemicals, viruses and bacteria); another peculiar property of gingiva is its rapid wound-healing process and the absence of scarring. Here we investigated the phenotype and the possible function of mesenchymal stem cells isolated from gingival papilla. Methods: MSCs have been isolated from gingival papilla (GinPa-MSCs) of donors undergoing oral surgery [1]. Primary cultures were analyzed for their proliferation rate, clonogenicity, mesenchymal stem cell marker expression [2] and multi-differentiative ability towards mesodermal lineages. Subsequently, we focused our research on the possible use of GinPa-MSCs as vehicles for drug delivery. Results: All the GinPa-MSCs showed a fibroblast-like morphology and a high proliferation rate (DT = 50.4±16.1 hours) that allowed us to rapidly collect a large number of cells. GinPa-MSCs displayed a high clonogenic potential (~20%) and expressed on their surface CD73, CD90, CD105 (>99%) and CD14 (~32%) while lacked CD45. CD14 mild surface expression and the abundance of pinocytotic structures, as revealed by TEM analysis, may be related to GinPa-MSC functional activity of active defence in the oral environment. When induced to differentiate towards osteogenic lineage, GinPa-MSCs increased collagen production (+79%) and extracellular calcified matrix deposition (+100%) respect to control cells, despite their high basal ALP activity. Preliminary data also indicated that GinPa-MSCs possess a mild chondrogenic potential, while lipid droplets, following adipogenic stimuli, were poorly detectable. After being tested for their sensitivity to the compound, GinPa-MSCs were primed with the chemotherapy drug Paclitaxel (PTX). Our results show that GinPa-MSCs do not metabolize or inactivate PTX and they can up-take and release it in an amount able to inhibit in vitro the growth of CFPAC-1 carcinoma cells. Conclusions: Our data indicate that GinPa-MSCs display peculiar characteristics that could be related to their unique functions of tissue regeneration and insult defence within the oral environment. Furthermore, their ability to uptake and release PTX represents an interesting perspective for drug delivery approaches to treat cancer and other pathologies related to the odontostomatological apparatus. Taken together, our results suggest that gingival stromal cells represent an attractive candidate in maxillo-facial and dental regenerative medicine. 1. Sonoyama W, Liu Y. PLoS One 2006; Dec 20;1:e79. 2. Dominici M, Le Blanc K. Cytotherapy 2006;8(4):315-17.