Development of novel therapy for lipodystrophy and obesity using human iPS cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 25461347
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kyoto University
• Principal Investigator: Noguchi Michio 京都大学, 医学研究科, 講師 (00432394)
• Co-Investigator(Renkei-kenkyūsha): SAKURAI Hidetoshi 京都大学, iPS細胞研究所, 准教授 (80528745) ; TAKAHASHI Kazutoshi 京都大学, iPS細胞研究所, 講師 (80432326) ; EBIHARA Ken 自治医科大学, 医学部, 准教授 (70362514)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: ヒトiPS細胞 / 脂肪萎縮症 / 肥満症

Outline of Final Research Achievements

Human iPS and ES cells have adipogenic potentials in vitro. Matrigel containing adipocyte-like cells derived from human iPS and ES cells was transplanted into the subcutaneous tissue of nude mice for 1-4 weeks. Histological analyses and gene expression analyses revealed the presence of adipocyte-like cells at 1-4 weeks. These cells can survive and maintain the differentiated properties of the adipocytes for at least 4 weeks after the transplantation. Then, iPS cells were generated from 5 patients with congenital generalized lipodystrophy, 2 patients with acquired generalized lipodystrophy and a patient with familial partial lipodystrophy. Among them, iPS cells from lipodystrophic patients with BSCL2 nonsense mutations (BSCL2-iPS cells) exhibited marked reduction of lipid droplet formation after adipogenic differentiation, compared with those from healthy subjects. BSCL2-iPS cells could provide valuable models with which to study the pathophysiology of lipodystrophy.

Free Research Field

糖尿病・内分泌