Gingiva-derived Stromal Cells Isolated from Cats Affected with Tooth Resorption Exhibit Increased Apoptosis, Inflammation, and Oxidative Stress while Experiencing Deteriorated Expansion and Anti-Oxidative Defense

Gingiva-derived mesenchymal stromal cells (GMSCs) are multipotent cells characterized by multilineage differentiation potential, proliferative expansion, and unique immunomodulatory ability, making them attractive as a new treatment of periodontal regeneration. In this study, GMSCs obtained from the gingiva of healthy cats (HE) as well as from cats affected by tooth resorption (TR) were isolated and characterized. Feline GMSCs (fGMSCs) from HE patients exhibited fibroblast-like morphology, developed cellular body, specific growth pattern, high expansion, and proliferative potential as well as reduced senescence signature. fGMSCs demonstrated high s-100 and IL-10 positive cells, while simultaneously having low activity of IL-1. Moreover, high activity of ki-67 combined with reduced senescence markers were noted. In comparison, GMSCs from cats with TR exhibited enlarged nuclei and flat, irregular shape along with increased expression of CD44, s-100 and CD45 and downregulation of CD73. GMSCs from TR cats showed lower ability to form colonies, increased incidence of apoptosis, higher number of senescent cells, and reduced cell migration. Upregulation of pro-inflammatory cytokines was also noted in the TR group along with lower expression of mTOR and miR-17 and upregulation of miR-378. Mitochondrial dynamics, biogenesis and antioxidant properties are also negatively impacted in this group. Collectively, our findings suggest that GMSCs isolated from the gingiva of cats affected with TR have deteriorated functionality caused by impaired proliferation and growth and possibly mediated via mitochondrial dysfunction. fGMSCs or their EV’s should be further investigated for their role in the pathophysiology of TR in cats. Graphical Abstract