Generation of iPS cells from PAI-1 deficient patient and differentiation into mature cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591420
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: SANO Hideto 浜松医科大学, 医学部, 助教 (80623842)
• Co-Investigator(Kenkyū-buntansha): URANO Tetsumei 浜松医科大学, 医学部, 教授 (50193967) ; SUZUKI Yuko 浜松医科大学, 医学部, 准教授 (20345812)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: PAI-1 / iPS cells / endothelial cells / angiogenesis / 凝固・線溶

Outline of Final Research Achievements

We have identified two independent PAI-1 deficient patients having apparent phenotypes of severe bleeding and impaired wound healing, both of which are not seen in the PAI-1 deficient mice. To investigate the intrinsic function of PAI-1 in different cell types, iPS cells from the patients were generated, and their phenotypes have been analyzed after being differentiated to mature cells. We have first differentiated the iPS cells to endothelial cells. The expression of Dll4 gene, known to be associated with the angiogenic development, was increased and the branching in the tube formation was reduced in PAI-1 deficient iPS derived endothelial cells (PAI-1 iPS-ECs). Furthermore, PAI-1 iPS-ECs were detached from dish-bottom more easily than control iPS-ECs when the cells were cultured on gelatin-coated dishes. These results suggest that PAI-1 could play critical roles in differentiation and maturation of endothelial cells.

Free Research Field

細胞生物学