Yoshiaki Takahashi1, Ratih Yuniartha1, Takayoshi Yamaza2, Soichiro Sonoda3, Haruyoshi Yamaza4, Kosuke Kirino1, Koichiro Yoshimaru1, Toshiharu Matsuura1, Tomoaki Taguchi1. 1. Department of Pediatric Surgery, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan. 2. Division of Oral Biological Sciences, Department of Molecular Cell Biology and Oral Anatomy, Graduate School of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. yamazata@dent.kyushu-u.ac.jp. 3. Division of Oral Biological Sciences, Department of Molecular Cell Biology and Oral Anatomy, Graduate School of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. 4. Department of Pediatric Dentistry, Division of Oral Health, Growth, and Development, Graduate School of Dental Science, Kyushu University, Fukuoka, Japan.
Abstract
PURPOSE: Mesenchymal stem cell (MSC)-based cell therapies have emerged as a promising treatment option for various diseases. Due to the superior survival and higher differentiation efficiency, three-dimensional spheroid culture systems have been an important topic of MSC research. Stem cells from human exfoliated deciduous teeth (SHED) have been considered an ideal source of MSCs for regenerative medicine. Thus, in the present study, we introduce our newly developed method for fabricating SHED-based micro-hepatic tissues, and demonstrate the therapeutic effects of SHED-based micro-hepatic tissues in mouse disease models. METHODS: SHED-converted hepatocyte-like cells (SHED-HLCs) were used for fabricating spherical micro-hepatic tissues. The SHED-HLC-based spheroids were then transplanted both into the liver of mice with CCl4-induced chronic liver fibrosis and the kidney of factor VIII (F8)-knock-out mice. At 4 weeks after transplantation, the therapeutic efficacy was investigated. RESULTS: Intrahepatic transplantation of SHED-HLC-spheroids improved the liver dysfunction in association with anti-fibrosis effects in CCl4-treated mice. Transplanted SHED-converted cells were successfully engrafted in the recipient liver. Meanwhile, renal capsular transplantation of the SHED-HLC-spheroids significantly extended the bleeding time in F8-knock-out mice. CONCLUSIONS: These findings suggest that SHED-HLC-based micro-hepatic tissues might be a promising source for treating pediatric refractory diseases, including chronic liver fibrosis and hemophilia A.
PURPOSE: Mesenchymal stem cell (MSC)-based cell therapies have emerged as a promising treatment option for various diseases. Due to the superior survival and higher differentiation efficiency, three-dimensional spheroid culture systems have been an important topic of MSC research. Stem cells from human exfoliated deciduous teeth (SHED) have been considered an ideal source of MSCs for regenerative medicine. Thus, in the present study, we introduce our newly developed method for fabricating SHED-based micro-hepatic tissues, and demonstrate the therapeutic effects of SHED-based micro-hepatic tissues in mouse disease models. METHODS: SHED-converted hepatocyte-like cells (SHED-HLCs) were used for fabricating spherical micro-hepatic tissues. The SHED-HLC-based spheroids were then transplanted both into the liver of mice with CCl4-induced chronic liver fibrosis and the kidney of factor VIII (F8)-knock-out mice. At 4 weeks after transplantation, the therapeutic efficacy was investigated. RESULTS: Intrahepatic transplantation of SHED-HLC-spheroids improved the liver dysfunction in association with anti-fibrosis effects in CCl4-treated mice. Transplanted SHED-converted cells were successfully engrafted in the recipient liver. Meanwhile, renal capsular transplantation of the SHED-HLC-spheroids significantly extended the bleeding time in F8-knock-out mice. CONCLUSIONS: These findings suggest that SHED-HLC-based micro-hepatic tissues might be a promising source for treating pediatric refractory diseases, including chronic liver fibrosis and hemophilia A.
Authors: Masako Miura; Stan Gronthos; Mingrui Zhao; Bai Lu; Larry W Fisher; Pamela Gehron Robey; Songtao Shi Journal: Proc Natl Acad Sci U S A Date: 2003-04-25 Impact factor: 11.205
Authors: Kazuo Ohashi; Jacob M Waugh; Michael D Dake; Takashi Yokoyama; Hiroyuki Kuge; Yoshiyuki Nakajima; Masaki Yamanouchi; Hiroyuki Naka; Akira Yoshioka; Mark A Kay Journal: Hepatology Date: 2005-01 Impact factor: 17.425
Authors: Lena Kastl; Sven Sauer; Tim Beissbarth; Michael Becker; Peter Krammer; Karsten Gülow Journal: Free Radic Biol Med Date: 2014-12-10 Impact factor: 7.376
Authors: Petra Koudelkova; Victor Costina; Gerhard Weber; Steven Dooley; Peter Findeisen; Peter Winter; Rahul Agarwal; Karin Schlangen; Wolfgang Mikulits Journal: Int J Mol Sci Date: 2017-10-10 Impact factor: 5.923