Researches using iPS cells on intractable respiratory diseases to elucidate their pathogenesis and develop novel therapy.

2014 Fiscal Year Final Research Report

• Project/Area Number: 22249031
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Kyoto University
• Principal Investigator: MISHIMA MICHIAKI 京都大学, 医学(系)研究科(研究院), 教授 (60190625)
• Co-Investigator(Kenkyū-buntansha): OGAWA Emiko 滋賀医科大学, 学内共同利用施設等, 講師 (00378671) ; SEYAMA Kuniaki 順天堂大学, 医学部, 准教授 (10226681) ; HANDA Tomohiro 京都大学, 医学研究科, 助教 (10432395) ; HIRAI Toyohiro 京都大学, 医学研究科, 准教授 (20359805) ; ITO Isao 京都大学, 医学研究科, 特定病院助教 (40447975) ; MURO Shigeo 京都大学, 医学研究科, 講師 (60344454) ; MATSUMOTO Hisako 京都大学, 医学研究科, 助教 (60359809) ; HEIKE Toshio 京都大学, 医学研究科, 教授 (90190173) ; CHIN Kazuo 京都大学, 医学研究科, 特定教授 (90197640)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Keywords: iPS細胞 / ES細胞 / II型肺胞上皮細胞 / surfactant protein C / carboxypeptidase M / ３次元培養 / Hermansky-Pudlak 症候群 / 嚢胞性線維症

Outline of Final Research Achievements

In this project, we focused on establishing methods to induce alveolar type II cells from human iPS/ES cells. First, in the stepwise induction of NKX2-1-positive “ventralized” anterior foregut endoderm cells (VAFECs), we identified carboxypeptidase M (CPM) as a surface marker of the cells and fetal human and murine lungs. CPM-positive cells were successfully purified from VAFECs. To overcome difficulty in determining surfactant protein-C positive cells, we generated SFTPC-GFP reporter human iPS cells. Using the reporter cells, a three-dimensional co-culture with fetal human lung fibroblasts was performed. CPM-positive cells purified from VAFECs differentiated into GFP-positive alveolar type II cells within spheroid structures, showing lamellar body-like structures by electron microscopy.
We generated disease specific human iPS cells of Hermansky-Pudlak syndrome and cystic fibrosis.

Free Research Field

医歯薬学