Dental pulp stem cells osteoarthritis

: Description of ovine dental pulp stem cells characteristics, stemness and in vitro immunomodulatory effect

Abstract

Background Osteoarthritis (OA) is a joint disease affecting a growing number of patients worldwide for which no treatment is currently available to cure or reverse the damages. Stem cell-based regenerative therapies are under investigation for their ability to repair of the damaged joint tissues as well as to reduce the pain symptoms and the joint’s inflammation. Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cells (MSCs) proposed as OA’s therapeutics. Before considering their clinical application, DPSCs safety and efficacy need to be tested in animal models.
Aim To study the potential of ovine DPSCs as an OA treatment, through description of the sheep’s dental pulp, as well as the description of ovine DPSCs: collection, expansion, characterization of stemness markers, and investigation of ovine DPSCs immunomodulatory capacities in vitro.
Methods Sheep incisors’ dental pulp cavities were measured using computed-tomography scan and histology, and compared to highlight the effect of age, and tooth position on the amount of dental pulp. Characterization of oDPSCs was conducted using the tri-lineage differentiation and MSCs markers expression as recommended by the ISCT. Novel markers specific to human DPSCs were also investigated. Ovine dermal fibroblasts were used as controls (differentiated cells). Finally, DPSCs immunomodulatory effect was measured in a LPS model of systemic inflammation, measuring DPSCs expression of pro- and anti-inflammatory cytokines.
Results Our CT-scan results suggested a significantly larger amount of dental pulp in the first and second incisor of sheep aged of two to three years old. DPSCs characterization was not able to confirm their stem cell identity as fibroblast showcased no significant differences in markers expression except for CD73, CD146, and CD34. Finally, DPSCs’ incubation in LPS led to the increased release of IL-6, a cytokine that could act as both a pro- and anti-inflammatory mediator of OA.
Conclusion Further characterization of ovine DPSCs is required before testing their therapeutic effect on OA, in vivo, in the sheep. However, preliminary results suggest DPSCs to have a similar immunomodulatory ability to humans, and raise high expectation toward this model.

Date of Award	18 Jan 2022
Original language	English
Awarding Institution	University of Namur
Supervisor	Jean-Michel Vandeweerd (Supervisor) & Fanny Hontoir (Co-Supervisor)