Chronological and Replicative Aging of CD51⁺/PDGFR-α⁺ Pulp Stromal Cells

As a crucial source of mesenchymal stromal cells, CD51⁺/PDGFR-α⁺ human dental pulp stromal cells (hDPSCs) are promising seeding cells for regenerative medicine. Cellular senescence hinders the translational application of hDPSCs. However, it remains unclear whether chronological and replicative senescence results in distinct outcomes for hDPSCs. To investigate the influence of senescence on DPSCs, we used transgenic lineage tracking, immunofluorescence, flow cytometry, and various molecular experiments to depict the dynamic pattern of hDPSCs in mice and humans during chronological and replicative senescence. The data demonstrated that CD51⁺/PDGFR-α⁺ cells were decreased in chronological senescence. Impaired self-renewal and higher ossificatory differentiation were observed in chronologically senescent hDPSCs. Regarding replicative senescence, a decreased CD51⁺ but upregulated PDGFR-α⁺ population was observed in culture. Furthermore, weakened self-renewal and osteogenic differentiation were observed in replicatively senescent hDPSCs. In summary, CD51⁺/PDGFR-α⁺ hDPSCs decrease in chronologically aged pulp, with self-renewal that is impaired without impaired osteogenic differentiation. However, replicative senescence has a different impact: self-renewal and ossific differentiation are impaired and CD51 expression is reduced, but PDGFR-α expression remains. These findings demonstrate the different outcomes of chronological and replicative senescence in CD51⁺/PDGFR-α⁺ hDPSCs. Furthermore, we revealed that impaired self-renewal is the core dysfunction for both types of cellular aging and that osteogenic differentiation capability differs between them. This study provides insights into the influence of chronological and replicative senescence on the characteristics and capabilities of hDPSCs. These advances provide fundamental knowledge to alleviate cellular aging of CD51⁺/PDGFR-α⁺ hDPSCs and promote their translational applications.