Apoptotic periodontal ligament stem cells combined with developmental endothelial locus-1 counteract experimental periodontitis with type 2 diabetes mellitus

Stem cell therapy has been utilized in the treatment of periodontitis. Recent studies have demonstrated that treatment with apoptotic mesenchymal stem cells (MSCs) exhibits immunomodulatory effects comparable to those of living MSCs. However, the effect of type 2 diabetes mellitus (T2DM) on the efficacy of apoptotic MSCs therapy for periodontitis remains poorly understood. In this study, a ligature-induced experimental periodontitis model was established in wild-type (WT) and db/db mice, followed by the injection of exogenous apoptotic periodontal ligament stem cells (PDLSCs). The results revealed suboptimal therapeutic outcomes with apoptotic PDLSCs in db/db mice. It was observed that the progression of periodontitis was associated with a reduction in the expression of developmental endothelial locus-1 (DEL-1) in experimental periodontitis model. Additionally, the expression of DEL-1 was partially restored during the resolution phase of inflammation. T2DM mice exhibited exacerbated alveolar bone loss and suppressed regeneration, accompanied by the inhibition of DEL-1 expression. In co-culture experiments, impaired macrophage efferocytosis of apoptotic PDLSCs was ameliorated by the addition of exogenous DEL-1 under lipopolysaccharide and high glucose conditions. Moreover, the co-administration of exogenous DEL-1 enhanced the therapeutic efficacy of exogenous apoptotic PDLSCs in db/db mice. In conclusion, diminished DEL-1 expression and impaired macrophage efferocytosis constrain the therapeutic potential of exogenous apoptotic PDLSCs in periodontitis with T2DM. The diminished therapeutic efficacy may be alleviated by the combination of exogenous DEL-1 and apoptotic PDLSCs, offering novel insights into potential therapeutic strategies for periodontitis with T2DM.