Novel cell therapy for diabetes with chemically-induced brown adipocytes

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17990
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Kotani Shin-Ichiro 京都府立医科大学, 医学部, 研究員 (30783964)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 糖尿病 / 移植・再生医療

Outline of Final Research Achievements

Brown adipocytes control carbohydrate and lipid metabolism as well as regulation of body temperature by dissipating excess energy as heat. In diabetic patients, their functions are almost lost. If brown adipocytes can be induced from somatic cells of the patients and transplanted back into them, such a strategy could be a novel and effective regeneration therapy. Recently, we have found a new method to directly convert human dermal fibroblasts into brown adipocytes by culturing with a small molecular compound. The converted cells strongly expressed brown adipocyte-specific genes and proteins. In addition, they are free from any exogenous genes and did not show tumorigenicity in mice so far tested. But their functions as brown adipocytes have not been fully characterized, and the mechanism of conversion remains to be clarified. In this study, we analyzed the functions of the directly converted brown adipocytes and explored the mechanism of direct conversion.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

これまでに我々の研究室では、遺伝子導入を用いて線維芽細胞を褐色脂肪細胞に直接転換させる技術も開発し、得られた細胞を糖尿病モデルマウスに移植するとインスリン抵抗性と脂質異常症を改善できることを報告したが、本技術で作出される褐色脂肪細胞は、機能的であるとともに、遺伝子を導入せずに小分子化合物を添加して培養するだけで短期間に調製できるため、再生医療への応用においてより有用であると考えられる。本研究でこの細胞の機能的特性を解析したことにより、その可能性がさらに高まった。また、コンヴァージョン機構の解析によって、褐色脂肪細胞への直接転換機序解明に近づいた。