Abstract

Introduction Periodontal ligament stem cells (PDLSCs) are commonly used in regenerating damaged periodontal tissues. The regeneration of complex periodontal tissues relies on stem cell crosstalk. Typically, bone marrow mesenchymal stem cells (BMMSCs) are used to promote the differentiation of PDLSCs. However, it is currently unknown whether BMMSCs have tissue-specific characteristic in promoting the differentiation of PDLSCs. Objectives To explore the differential effects of BMMSCs from different sources on the potential of PDLSCs for the regeneration of periodontal tissue defects. Methods PDLSCs were cocultured with BMMSCs from different sources or their extracellular vesicles (EVs) in vitro. Osteogenic/cementogenic-related markers were observed to identify differences in the differentiation of PDLSCs subjected to different treatments. PDLSCs subjected to different treatments were combined with ceramic hydroxyapatite, which were then implanted subcutaneously into nude mice or repair the periodontal tissue defects in beagle dogs. The ectopic formation of hard tissues and the efficacy of the in situ repair of composite periodontal structures by the cell sheets were also observed. Results The indirect coculture of PDLSCs with BMMSCs derived from the jawbone (jBMMSCs) resulted in a significant increase in differentiation. The effects of indirect coculture of PDLSCs with jBMMSCs on the subcutaneous differentiation into hard tissues in nude mice and the regeneration of periodontal defects in beagle dogs in situ were also superior to that of BMMSCs derived from iliac bone. The inhibition of EV secretion by BMMSCs weakened the ability of BMMSCs to promote PDLSC differentiation. EVs derived from jBMMSCs more effectively promoted PDLSC differentiation in vitro, and the in situ functional repair of periodontal defects. Conclusions jBMMSCs can better promote PDLSC differentiation and the repair of periodontal defects through paracrine EVs. The results of this study provide an