Antibacterial periodontal ligament stem cells enhance periodontal regeneration and regulate the oral microbiome.

BACKGROUND: The transplantation of periodontal ligament stem cells (PDLSCs) has been shown to enhance periodontal regeneration in animal models and clinical trials. However, it is not known whether PDLSCs are antibacterial and whether this affects oral microbiota and periodontal regeneration. METHODS: We isolated human PDLSCs from periodontal ligament of extracted teeth. Rats' periodontal fenestration defects were prepared, and treated with PDLSC injections (Cell group), using saline injections (Saline group) as the control. The oral microbiota was explored by 16 S rDNA sequencing and compared with that before surgery (PRE group). The antibacterial property of PDLSCs and its underlying mechanism were tested in vitro. RESULTS: Microbiome analyses reveal a decreased biodiversity, a changed community structure, and downregulated community functions of the oral microbiome in the Saline group. PDLSCs injections enhance periodontal regeneration, reverse the decrease in diversity, and increase the abundance of non-pathogenic bacterial Bifidobacterium sp. and Lactobacillus sp., making the oral microbiome similar to that of the PRE group. In vitro, PDLSCs inhibit the growth of Staphylococcus aureus, Escherichia coli, and Fusobacterium nucleatum. The main mechanism of action is postulated to involve production of the cationic antimicrobial peptide LL-37. CONCLUSIONS: Our findings reveal that PDLSC injections enhance periodontal regeneration and regulate the oral microbiome to foster an oral cavity microenvironment conducive to symbiotic microbiota associated with health.