Regenerative therapy for metabolic diseases based on chemical direct reprogramming

• Project/Area Number: 26670452
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: OSAM Mazda 京都府立医科大学, 医学(系)研究科(研究院), 教授 (00271164)
• Co-Investigator(Renkei-kenkyūsha): KAWAHITO Utaka 京都府立医科大学, 医学研究科, 准教授 (50336731)
• Research Collaborator: KISHIDA Tsunao 京都府立医科大学, 准教授 (00370205) ; OHGITANI Eriko 京都府立医科大学, 医学研究科, 助教 (80300820) ; WATANABE Eri 京都府立医科大学, 助教 (20433253) ; SHIN-YA Masaharu 京都府立医科大学, プロジェクト研究員 (10405277) ; KIYOSHI Kazunari 京都大学, 工学研究科, 教授 (90201285) ; KITABATAKE Yasuji 大阪大学, 医学系研究科, 助教 (80506494)
• Project Period (FY): 2014-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: 糖脂質代謝

Outline of Final Research Achievements

Brown adipocytes (BAs) expend energy as heat. Recently we succeeded in directly inducing human brown adipocytes from the fibroblasts. Here we aimed at establishing a direct reprogramming procedure to obtain brown adipocytes from fibroblasts by means of small chemical compounds. We established a high-sensitivity and high-throughput screening system and screened a chemical library. As result we found some candidates that satisfied screening criteria. The present study may contribute to understanding of differentiation of brown adipocytes, while it may also lead to novel regenerative therapy for metabolic diseases.

Research Products

• [Journal Article] Direct conversion of human fibroblasts into functional osteoblasts by defined factors (2015)
  • Author(s): Yamamoto K. et al.
  • Journal Title: Proc Natl Acad Sci USA Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Pleiotropic functions of magnetic nanoparticles for ex vivo gene transfer. (2014)
  • Author(s): Kami D, Kitani T, Kishida T, Mazda O, Toyoda M, Tomitaka A, Ota S, Ishii R, Takemura Y, Watanabe M, Umezawa A, Gojo S.
  • Journal Title: Nanomedicine Volume: 10 Issue: 6 Pages: 1165-1174
  • DOI: 10.1016/j.nano.2014.03.018
  • Peer Reviewed / Open Access
• [Journal Article] HIF-1α-induced HSP70 regulates anabolic responses in articular chondrocytes under hypoxic conditions (2014)
  • Author(s): Tsuchida S, Arai Y, Takahashi KA, Kishida T, Terauchi R, Honjo K, Nakagawa S, Inoue H, Ikoma K, Ueshima K, Matsuki T, Mazda O, Kubo T
  • Journal Title: J Orthop Res Volume: (Epub ahead of print) Issue: 8 Pages: 975-980
  • DOI: 10.1002/jor.22623
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/24677016
  • Peer Reviewed / Open Access
• [Journal Article] Cycloamylose-Nanogel DDS-mediated intratumor silencing of the vascular endothelial growth factor regulates neovascularization in tumor microenvironment (2014)
  • Author(s): H. Fujii, M. Shin-Ya, S. Takeda, Y. Hashimoto, S. Mukai, S. Sawada, T. Adachi, K. Akiyoshi, T. Miki, O. Mazda
  • Journal Title: Cancer Science Volume: 105 Issue: 12 Pages: 1616-1625
  • DOI: 10.1111/cas.12547
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Inhibition of osteoclastogenesis by osteoblast-like cells genetically engineered to produce interleukin-10 (2014)
  • Author(s): Fujioka K et al.
  • Journal Title: Biochem Biophys Res Commun Volume: 456 Issue: 3 Pages: 785-791
  • DOI: 10.1016/j.bbrc.2014.12.040
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Direct reprogramming of functional human osteoblasts for periodontal tissue regeneration (2015)
  • Author(s): Yamamoto K. et al.
  • Organizer: 93th General Session & Exhibition of the IADR
  • Place of Presentation: Boston
  • Year and Date: 2015-03-11 – 2015-03-14
• [Presentation] Directly reprogrammed osteoblasts genetically engineered to produce interleukin-10 significantly suppress osteoclastogenesis. (2014)
  • Author(s): Fujioka K. et al.
  • Organizer: EULAR congress 2014
  • Place of Presentation: Paris
  • Year and Date: 2014-06-14