In vitro evaluation of periapical lesion‐derived stem cells for dental pulp tissue engineering

Abstract

Dental pulp tissue engineering is a promising alternative treatment for pulpitis and periapical periodontitis, and dental pulp stem cells (DPSCs) are considered to be the gold standard for dental seed cell research. Periapical lesions harbor mesenchymal stem cells with the capacity for self‐renewal and multilineage differentiation. However, it remains unknown whether these periapical lesion‐derived stem cells (PLDSCs) are suitable for dental pulp tissue engineering. To investigate this possibility, PLDSCs and DPSCs were isolated using the tissue outgrowth method and cultured under identical conditions. We then performed in vitro experiments to investigate their biological characteristics. Our results indicate that PLDSCs proliferate actively in vitro and exhibit similar morphology, immunophenotype and multilineage differentiation ability as DPSCs. Simultaneously, PLDSCs exhibit stronger migrative ability and express more vascular endothelial growth factor and glial cell line‐derived neurotrophic factor than DPSCs, and PLDSC‐derived conditioned medium was more effective in tube formation assay. The mRNA expression levels of immunomodulatory genes HLA‐G , IDO and ICAM‐1 were also higher in PLDSCs. However, regarding osteo/odontogenic differentiation, PLDSCs showed weaker alkaline phosphatase staining and lower calcified nodule formation compared to DPSCs, as well as lower expression of ALP , RUNX2 and DSPP , as confirmed by a quantitative RT‐PCR. The osteo/odontogenic protein expression levels of DSPP, RUNX2, DMP1 and SP7 were also higher in DPSCs. The present study demonstrates that PLDSCs demonstrate potential use as seed cells for dental pulp regeneration, especially for achieving enhanced neurovascularization.

Periapical lesion-derived decellularized extracellular matrix as a potential solution for regenerative endodontics

“…Different from many reports on the use of DPSCs for pulp regeneration, and considering the difficulties in obtaining homologous MSCs for clinical application, we selected PLDSCs with multi-lineage differentiation ability, which enriches perspective for the source and subsequent application of maxillofacial related stem cells. The single-cell sequencing of apical periodontitis identified PLDSCs as four different subclusters: osteolineage, endothelial, inflammatory and neurological MSCs, indicating more advantageous in angiogenic and neural differentiation to serve as seed cells for tissue regeneration [ 27 , 38 ].…”

“…The mesenchymal stem cells (MSCs) from periapical lesions are prone to differentiate into osteoblast lineage cells under the stimulation of apical periodontitis [ 27 ]. Our research group has also discovered that PLDSCs exhibit less osteogenic/odontoblast differentiation ability compared to DPSCs, but they possess a more vital capability to secrete neurovascular factors and regulate the immune responses, making them potential candidates for tissue engineering of dental pulp [ 38 , 39 ].…”

Bioceramics in Endodontics: Updates and Future Perspectives

“…Since dental stem cells can promote root development, some strategies are used to treat young permanent teeth with pulp necrosis but incomplete root development [ 196 , 197 , 198 ]. Apexification and regenerative endodontic therapy are effective options for periapical tissue healing and open apical closure [ 199 , 200 , 201 , 202 ].…”

Mesenchymal Stem Cells Derived from Human Periapical Cysts and Their Implications in Regenerative Medicine

“…Also, another appealing approach in the research field is represented by the affinity of the hPCy-MSCs towards the development of neuron-like cells and their use in degenerative disorders [ 62 , 63 ]. Li et al [ 64 ] conducted a study aiming to compare the properties of the periapical lesions derived from MSCs and from the DPSCs. They evaluated the differentiation potential, the immunomodulatory properties and the pro-angiogenesis ability.…”