Direct differentiation of progenitor stem-like cells into mesenchymal stem, and osteogenic cells


Epithelial cell rests of Malassez derived from the periodontal ligament were transformed into progenitor stem-like cells by stimulation with epigenetic agents.

Subsequently, the progenitor stem-like cells were directly differentiated into endothelial, mesenchymal stem, and osteogenic cells that constitute the periodontal ligament.


Stem cells derived from the dental pulp or periodontal ligament have been used for regenerative dentistry. Although it is relatively easy to collect the dental pulp stem cells, it is difficult to obtain adequate numbers of good quality cells; a stable supply is required for their application in regenerative dentistry. In the present study, we generated the progenitor-stem-like cells from ERM cells in the periodontal ligament using the epigenetic modifications without gene transfer. The progenitor stem-like cells were differentiated into endothelial, mesenchymal stem, and osteogenic cells--which constitute the periodontal ligament--using a direct reprogramming method that induces the differentiation of progenitor stem cells into the target cells.

Methods and results

The isolated ERM cells were induced to differentiate into progenitor stem-like cells, which were similar to stem cells, following stimulation with the epigenetic agents, 5-Azacytidine and Valproic acid, for 1 week. The progenitor stem-like cells expressed the protein stem cell markers NANOG and OCT3/4, which were also observed in the iPS cells.

The progenitor stem-like cells were differentiated into endothelial, mesenchymal stem, and osteogenic cells. The expression of the specific marker for each cell type was confirmed.

Future prospects

The findings of the present study may contribute to the development of new periodontal regenerative therapy. Epigenetic agents have been successfully applied in various human diseases, including cancers. Nonetheless, further investigations are needed to confirm the findings of this study.

Journal reference:

Yoshida, K., et al. (2021) Direct reprogramming of epithelial cell rests of malassez into mesenchymal-like cells by epigenetic agents. Scientific Reports.


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