In vivo regenerative treatment of interstitial cystitis by direct reprogramming

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09377
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Inoue Yuta 京都府立医科大学, 医学(系)研究科(研究院), 助教 (20898499)
• Co-Investigator(Kenkyū-buntansha): 松田 修 京都府立医科大学, 医学(系)研究科(研究院), 教授 (00271164) ; 岸田 綱郎 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (00370205) ; 浮村 理 京都府立医科大学, 医学(系)研究科(研究院), 教授 (70275220)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: direct reprogramming / urothelial cell / human dermal fibroblast / bladder / interstitial cystitis / Hunner type / intravesical infusion

Outline of Final Research Achievements

Interstitial cystitis (Hunner type) is a disease that causes symptoms such as bladder pain and pollakiuria due to loss of urothelial cells or their functions, and is a designated intractable disease (No. 226) for which there is currently no effective treatment. Our research team has already reported that direct reprogramming from human dermal fibroblasts into urothelial cells was possible by introducing FOXA1, TP63, L-MYC, and KLF4. As the next step, we tried various methods of direct reprogramming of urothelial cells using only small molecule compounds that do not rely on gene induction by viral vectors. As a result, direct conversion using only small molecule compounds was not achieved at this time, and we will continue to investigate ways to establish a method. In addition, we have successfully created a interstitial cystitis mouse model by intravesical injection of H2O2, and will continue to investigate methods to regenerate the bladder urothelium in mice.

Free Research Field

Urology

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尿路上皮細胞に直接転換させる技術を開発し報告している。遺伝子導入によるダイレクト・リプログラミングは細胞の腫瘍化リスクが高くなり、臨床応用に際しては障壁が多い手法となる。そのため、遺伝子導入に依存せず、小分子化合物のみを用いて繊維芽細胞を尿路上皮細胞に直接転換させる手法を樹立し、現在根本的な治療のない間質性膀胱炎患者に対して新規治療を提供することが可能となり、膀胱再生医療に大きく寄与できると考えられる。