Periodontal tissue stem cells and mesenchymal stem cells in the periodontal ligament

Abstract

Periodontal tissue stem cells, which play a crucial role in maintaining the homeostasis of periodontal tissues, are found in the periodontal ligament (PDL). These cells have long been referred to as mesenchymal stem/stromal cells (MSCs), and their clinical applications have been extensively studied. However, tissue stem cells in the PDL have not been thoroughly investigated, and they may be different from MSCs. Recent advances in stem cell biology, such as genetic lineage tracing, identification of label-retaining cells, and single-cell transcriptome analysis, have made it possible to analyze tissue stem cells in the PDL in vivo. In this review, we summarize recent findings on these stem cell populations in PDL and discuss future research directions toward developing periodontal regenerative therapy.

Keywords: Mesenchymal stem/stromal cell; Periodontal ligament; Periodontal regeneration; Periodontal tissue; Tissue stem cell.

Fig. 1

Three lineages differentiated from PDLSC. E: Enamel, D: Dentin, C: Cementum, G: Gingiva, AB: Alveolar bone, PDL: Periodontal ligament, Fb: Fibroblast, Ob: Osteoblast, Cb: Cementoblast, PDLSC: Periodontal ligament stem cell.

Fig. 2

High and low osteogenic progenitors in PDL. A. Scatter plots of the mean FPKM values of transcription factors in high and low osteogenic clones calculated by RNA-seq analysis. The differentially expressed genes showing> 2-fold statistically significant differences are shown in purple. FPKM: fragments per kilobase of exon per million reads mapped. B. High osteogenic clones and Zbp-1 knockout clones were cultured in osteogenic medium and stained with Alizarin Red S on day 8 of differentiation induction.

Fig. 3

Lineage tracing strategy of the periodontal ligament. Genetic lineage tracing of the PDLSC requires double transgenic mice generated by crossing PDLSC-specific CreER^T2 and Cre reporter mouse lines. In the system, a fusion protein of a mutated estrogen receptor and Cre recombinase is expressed in PDLSC, and the two loxP sites in the reporter allele will undergo recombination once tamoxifen is administrated. Upon removal of the STOP sequence, the PDLSC expresses the fluorescent protein (e.g., tdTomato). Once PDLSC is marked, the mark is heritable and permanent and thus transmitted to all the descendants of PDLSC. PDLSCs: periodontal ligament stem cells, ATG: start codon; pA: polyadenylation signal sequence, STOP: stop cassette, FP: fluorescent protein, C: Cementum, AB: Alveolar bone, Fb: fibroblast, Ob: osteoblasts, Cb: cementoblasts.