LRRC15 expression indicates high level of stemness regulated by TWIST1 in mesenchymal stem cells

Kensuke Toriumi; Yuta Onodera; Toshiyuki Takehara; Tatsufumi Mori; Joe Hasei; Kanae Shigi; Natsumi Iwawaki; Toshifumi Ozaki; Masao Akagi; Mahito Nakanishi; Takeshi Teramura

doi:10.1016/j.isci.2023.106946

LRRC15 expression indicates high level of stemness regulated by TWIST1 in mesenchymal stem cells

iScience. 2023 May 23;26(7):106946. doi: 10.1016/j.isci.2023.106946. eCollection 2023 Jul 21.

Authors

Affiliations

¹ Department of Orthopedic Surgery, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, Japan.
² Institute of Advanced Clinical Medicine, Kindai University Hospital, Osaka-sayama, Osaka, Japan.
³ Life Science Institute, Kindai University, Osaka-sayama, Osaka, Japan.
⁴ Department of Orthopedic Surgery, Okayama University Faculty of Medicine, Okayama, Okayama, Japan.
⁵ Tokiwa Bio Inc, Tsukuba, Ibaraki, Japan.

Abstract

Mesenchymal stem cells (MSCs) are used as a major source for cell therapy, and its application is expanding in various diseases. On the other hand, reliable method to evaluate quality and therapeutic properties of MSC is limited. In this study, we focused on TWIST1 that is a transcription factor regulating stemness of MSCs and found that the transmembrane protein LRRC15 tightly correlated with the expression of TWIST1 and useful to expect TWIST1-regulated stemness of MSCs. The LRRC15-positive MSC populations in human and mouse bone marrow tissues highly expressed stemness-associated transcription factors and therapeutic cytokines, and showed better therapeutic effect in bleomycin-induced pulmonary fibrosis model mice. This study provides evidence for the important role of TWIST1 in the MSC stemness, and for the utility of the LRRC15 protein as a marker to estimate stem cell quality in MSCs before cell transplantation.

Keywords: Cell biology; Omics; Stem cells research; Transcriptomics.