MEST Regulates the Stemness of Human Periodontal Ligament Stem Cells

Daigaku Hasegawa; Kana Hasegawa; Hiroshi Kaneko; Shinichiro Yoshida; Hiromi Mitarai; Mai Arima; Atsushi Tomokiyo; Sayuri Hamano; Hideki Sugii; Naohisa Wada; Tamotsu Kiyoshima; Hidefumi Maeda

doi:10.1155/2020/9672673

MEST Regulates the Stemness of Human Periodontal Ligament Stem Cells

Stem Cells Int. 2020 Jul 8:2020:9672673. doi: 10.1155/2020/9672673. eCollection 2020.

Authors

Affiliations

¹ Department of Endodontology, Kyushu University Hospital, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
² Department of Oral Pathology, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
³ Department of Endodontology and Operative Dentistry, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
⁴ Division of General Dentistry, Kyushu University Hospital, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
⁵ OBT Research Center, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

Abstract

Periodontal ligament (PDL) stem cells (PDLSCs) have been reported as a useful cell source for periodontal tissue regeneration. However, one of the issues is the difficulty of obtaining a sufficient number of PDLSCs for clinical application because very few PDLSCs can be isolated from PDL tissue of donors. Therefore, we aimed to identify a specific factor that converts human PDL cells into stem-like cells. In this study, microarray analysis comparing the gene profiles of human PDLSC lines (2-14 and 2-23) with those of a cell line with a low differentiation potential (2-52) identified the imprinted gene mesoderm-specific transcript (MEST). MEST was expressed in the cytoplasm of 2-23 cells. Knockdown of MEST by siRNA in 2-23 cells inhibited the expression of stem cell markers, such as CD105, CD146, p75NTR, N-cadherin, and NANOG; the proliferative potential; and multidifferentiation capacity for osteoblasts, adipocytes, and chondrocytes. On the other hand, overexpression of MEST in 2-52 cells enhanced the expression of stem cell markers and PDL-related markers and the multidifferentiation capacity. In addition, MEST-overexpressing 2-52 cells exhibited a change in morphology from a spindle shape to a stem cell-like round shape that was similar to 2-14 and 2-23 cell morphologies. These results suggest that MEST plays a critical role in the maintenance of stemness in PDLSCs and converts PDL cells into PDLSC-like cells. Therefore, this study indicates that MEST may be a therapeutic factor for periodontal tissue regeneration by inducing PDLSCs.