YAMATO Masayuki
   Department   Research Institutes and Facilities, Research Institutes and Facilities
   Position   Professor
Article types Original article
Language English
Peer review Peer reviewed
Title Assessment of the Safety of Chondrocyte Sheet Implantation for Cartilage Regeneration.
Journal Formal name:Tissue engineering. Part C, Methods
Abbreviation:Tissue Eng Part C Methods
ISSN code:(1937-3392)1937-3384(Linking)
Domestic / ForeginForegin
Publisher Mary Ann Liebert, Inc
Volume, Issue, Page 22(1),pp.59-68
Author and coauthor YOKOYAMA Miyuki†, SATO Masato, UMEZAWA Akihiro, MITANI Genya, TAKAGAKI Tomonori, YOKOYAMA Munetaka, KAWAKE Tomoko, OKADA Eri, KOKUBO Mami, ITO Noriko, TAKAKU Yuko, MURAI Kunihiko, MATOBA Ryo, AKUTSU Hidenori, YAMATO Masayuki, OKANO Teruo, MOCHIDA Joji*
Publication date 2016/01
Summary We have previously studied the effects of chondrocyte sheets on the repair and regeneration of articular cartilage by using temperature-responsive culture inserts. On the basis of this work, we succeeded in rapid fabrication of chondrocyte sheets with the use of a coculture method in which inserts were placed between synoviocytes and chondrocytes. Treatment of cartilage defects using layered chondrocyte sheets promotes repair and regeneration; this method is compatible with in vivo osteoarthritis models that reproduce partial-thickness defects. In human stem cell clinical research guidelines, the Ministry of Health, Labour and Welfare (MHLW) approved several applications related to this technology. Indeed, its translation to a clinical setting is already yielding favorable results. In this study, we evaluated the risk of tumorigenesis associated with this treatment and characterized the dynamics of biological processes associated with the posttransplantation cell sheets in vivo. Furthermore, we also confirmed the safety of the procedure by using array comparative genomic hybridization (array CGH) and G-band staining to screen for deleterious genetic aberrations during prolonged subculture of cells. The safety of chondrocytes that were cultured for longer than normal was confirmed by the array CGH and G-band staining results. In addition, tumorigenicity testing confirmed that culture chondrocyte sheets are not tumorigenic. Furthermore, from the evaluation of bioluminescence imaging following implantation of the cell sheets, it was confirmed that the transplanted chondrocytes and synoviocytes remained in the knee joint and did not transfer elsewhere over time. We believe that the technique used in this study is a highly useful method for evaluating the safety of not only chondrocytes but also extensive subculturing in general.
DOI 10.1089/ten.TEC.2015.0254
PMID 26560184