Investigation of kidney microenvironment by cell reconstruction in vivo

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K15214
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: KANAI Masami 東京医科歯科大学, 統合研究機構, 教授 (70321883)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 再生 / ジフテリア毒素

Outline of Final Research Achievements

By use of the combination of human diphtheria toxin (DT) and its receptor, it is possible to kill the certain cells in vivo. We have succeed to development of transgenic lines to replace host cells to recipient new transgenic mose (Tg) line. We have tried to the combination of ROSA26-iDTR and Ltf (Lactoferrin)-iCre Tg. Ltf is expressed in seminal vesicles, epididymis and epithelial cells of the vas deferens in 60-day-old mature males. Administration of diphtheria toxin in this line made it possible to replace these epithelial cells after sexual maturation. We have succeeded in creating a system that allows xenogeneic cell transplantation using a new DT line.

Free Research Field

発生工学

Academic Significance and Societal Importance of the Research Achievements

精細管は管状の閉鎖空間で、比較的免疫寛容を受け易い環境を有する。AMH-Treck Tgマウス(GFP KI)や、Ltf/ROSA26-iDTRトランスジェニックマウスに中胚葉系上皮様細胞などの移植条件を決定し、その後、免疫寛容を呈するNODマウスへ遺伝背景のバッククロスすることで、ヒトiPS由来細胞異種細胞の移入しいては、xenotransplantationの確立へと展開させることが可能となる。将来的には、ヒトiPS細胞から腎各種細胞へのin vivo分化系の探索の糸口となり、その結果、社会的意義が大きいと思われる。