Effect of CD44 signal axis in the gain of mesenchymal stem cell surface antigens from synovial fibroblasts in vitro
Masaaki Isono,
Jun Takeuchi,
Ami Maehara,
Yusuke Nakagawa,
Hiroki Katagiri,
Kazumasa Miyatake,
Ichiro Sekiya,
Hideyuki Koga,
Yoshinori Asou,
Kunikazu Tsuji
Affiliations
Masaaki Isono
Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Jun Takeuchi
Medical Affairs Unit, Seikagaku Corporation, Tokyo, Japan
Ami Maehara
Department of Cartilage Regeneration, Tokyo Medical and Dental University, Tokyo, Japan; Department of Nano-Bioscience, Tokyo Medical and Dental University, Tokyo, Japan
Yusuke Nakagawa
Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo, Japan; Department of Cartilage Regeneration, Tokyo Medical and Dental University, Tokyo, Japan
Hiroki Katagiri
Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Kazumasa Miyatake
Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo, Japan; Department of Cartilage Regeneration, Tokyo Medical and Dental University, Tokyo, Japan
Ichiro Sekiya
Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Hideyuki Koga
Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Yoshinori Asou
Department of Nano-Bioscience, Tokyo Medical and Dental University, Tokyo, Japan
Kunikazu Tsuji
Department of Cartilage Regeneration, Tokyo Medical and Dental University, Tokyo, Japan; Department of Nano-Bioscience, Tokyo Medical and Dental University, Tokyo, Japan; Corresponding author.
Tissue-residing mesenchymal stromal/stem cells (MSCs) have multipotent characteristics that are important for adult tissue homeostasis and tissue regeneration after injury. We previously reported that fibroblastic cells isolated from the synovial membrane in the knee joint give rise to cells with MSC characteristics in a two-dimensional culture. To explore the molecular mechanisms underlying these hyperplastic properties, we performed time-course surface antigen expression analyses during in vitro culture. Cells freshly isolated from the synovial membrane rarely contained cells that met the criteria (CD45−CD73+CD90+CD105+). However, the number of cells expressing MSC antigens increased on day 7. Flow cytometric analysis indicated that cells positive for either CD73 or CD90 were specifically derived from cells positive for CD44. CD44 expression was upregulated during culture, and CD105+ cells were specifically derived from the CD44 highly expressing cells. In addition, depletion of hyaluronic acid (HA), a major ligand of CD44, decreased the number of CD105+ cells, whereas supplementation with HA increased their number. These data suggest that intracellular signals activated by CD44 play an important role in the formation and/or maintenance of MSCs.
