Generation of novel disease models and development of cell transplantation therapies using iPS cells derived from Fabry disease patients

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16624
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Kurume University
• Principal Investigator: Nasu Makoto 久留米大学, 医学部, 助教 (20441660)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Fabry病モデルマウス / iPS Cell / GLA遺伝子

Outline of Final Research Achievements

Hemi, hetero and homozygotes were successfully generated from Fabry disease model mice. It was possible to create Fabry disease mice from hemi and homozygotes. The model mice produced showed accumulation of globotriaosylceramide (Gb3) in the heart and kidneys. It was possible to induce differentiation into nephron progenitor cells in iPS cells derived from patients with Fabry disease and healthy individuals, respectively, as previously reported. Intracellular lysosomal accumulation, a hallmark of Fabry disease, was observed. Transplantation caused problems with viability and dropout was observed. In the future, we will use mouse iPS cells to infer pathogenesis-related molecules and search for novel therapeutic targets.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

iPS細胞より恒常的にα-Gal酵素を供給する腎構成細胞を作製する。そして、Fabry病モデルマウスに移植し、細胞種の違いによる生着能および酵素補充能を検証することで再生組織細胞を用いた根治的治療法を確立する。また、創出した疾患モデル組織の網羅的遺伝子発現解析から病態関連分子の同定を行い、新規治療標的を探索する。作製した細胞を移植することで、α-Gal酵素による根治的治療法を目指すものであり、これまでにない新規の治療法であることからFabry病患者にとって新たな希望となり得る。iPS細胞を用いた新規病態モデルの開発を行う本研究は、新規かつ独創的である。