Abstract
Pulp regeneration after transplantation of mobilized dental pulp stem cells (MDPSCs) declines in the aged dogs due in part to the chronic inflammation and/or cellular senescence. Eotaxin-1/C-C motif chemokine 11 (CCL11) is an inflammation marker via chemokine receptor 3 (CCR3). Moreover, CCR3 antagonist (CCR3A) can inhibit CCL11 binding to CCR3 and prevent CCL11/CCR3 signaling. The study aimed to examine the effect of CCR3A on cellular senescence and anti-inflammation/immunomodulation in human periodontal ligament cells (HPDLCs). The rejuvenating effects of CCR3A on neurite extension and migratory activity to promote pulp regeneration in aged dog teeth were also evaluated. In vivo, the amount of regenerated pulp tissues was significantly increased by transplantation of MDPSCs with CCR3A compared to control without CCR3A. In vitro, senescence of HPDLCs was induced after p-Cresol exposure, as indicated by increased cell size, decreased proliferation and increased senescence markers, p21 and IL-1β. Treatment of HPDLCs with CCR3A prevented the senescence effect of p-Cresol. Furthermore, CCR3A significantly decreased expression of CCL11, increased expression of immunomodulatory factor, IDO, and enhanced neurite extension and migratory activity. In conclusion, CCR3A protects against p-Cresol-induced cellular senescence and enhances rejuvenating effects, suggesting its potential utility to stimulate pulp regeneration in the aged teeth.
Highlights
Pulp regeneration after transplantation of mobilized dental pulp stem cells (MDPSCs) declines in the aged dogs due in part to the chronic inflammation and/or cellular senescence
Histological analysis of the microenvironment of aged teeth showed chronic inflammation in a form of fibrosis in periapical tissue compared to young dog teeth (Supplementary Fig. S1)[29] which might be a reason for the decline of pulp regeneration[9]
A larger amount of dentin was observed along the dentinal wall on day 60 compared with on day 14 in the regenerated pulp tissue which is promoted by CCR3 antagonist (CCR3A) (Fig. 1C,D)
Summary
Pulp regeneration after transplantation of mobilized dental pulp stem cells (MDPSCs) declines in the aged dogs due in part to the chronic inflammation and/or cellular senescence. CCR3A protects against p-Cresol-induced cellular senescence and enhances rejuvenating effects, suggesting its potential utility to stimulate pulp regeneration in the aged teeth. Transplanted mesenchymal stem cells (MSCs) have presented outstanding therapeutic efficacy in many preclinical/clinical disease models in terms of their growth and differentiation capabilities and trophic effects including proliferative, migratory, cell survival and immunomodulatory effects[4] It has been stated by several types of research that the regenerative capacity and naïve properties of MSCs to maintain tissue regeneration progressively decline with age and pathological conditions[5,6]. Reduced CCL11 expression by CCR3A and its rejuvenating effects on the migratory, angiogenesis and neurite outgrowth activities were examined
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