Establishment of novel diagnosis methods for hereditary nephrontubular diseases using the disease-specific iPS cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09659
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Nihon University
• Principal Investigator: HAKETA Akira 日本大学, 医学部, 助教 (60624294)
• Co-Investigator(Kenkyū-buntansha): 福田 昇 日本大学, 総合科学研究所, 教授 (40267050)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 疾患特異的iPS細胞 / 遺伝性尿細管疾患 / アクアポリン / 偽性副甲状腺機能低下症

Outline of Final Research Achievements

To develop in vitro parathyroid hormone (PTH) stimulating test, we will establish the disease (psudehyperparathyroid: PHP)-specific iPS cells from periferal blood mononuclear cells (MNC) of PHP patients and differenciate the PHP-specific iPS cells to nephrotunular cells on which we will perform the PTH stimulating test. iPS cell line (201B7) was differenciated to nephrotunular cells in matrigel with BMP2, BMP7, activin-A and retinoic acid. 201B7 cell line was differenciated to aquaporin-positive nephrotubular cells. Addition of PTH increased cAMP levels and incorporation of Phosphorus in RPTEC. We established iPS cells from MNCs from patients with PHP and confirmed diffarenciation to aquaporin-positive nephrotubular cells. We could completely eliminate the contamination of undiffareciated iPS cells with rBC2LCN-PE23. These findings indicate possibility of establishment of diagnosis of hereditary nephrotubular diseases by the disease-specific iPS cell technology.

Free Research Field

内分泌学

Academic Significance and Societal Importance of the Research Achievements

これまで遺伝性尿細管疾患、とりわけ偽性副甲状腺機能低下症の臨床的診断法であるEllsworth‐Howard試験でのPTHによる尿中cAMPとリン酸排泄の正確な評価は困難な事が多かった。今回の研究にて偽性副甲状腺機能低下症の疾患特異的iPS細胞からの培養尿細管細胞でPTH負荷によるcAMP増加とリン酸の細胞内取り込みにて、Ellsworth‐Howard試験をin vitroで行える事は大いに意義がある。予想される結果としては遺伝性尿細管疾患の正確な診断法が確立され、医療社会的意義も大きい。