Analysis of disease mechanism of growth impairment in Down syndrome using human iPS cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461643
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Osaka University
• Principal Investigator: ARAHORI HITOMI 大阪大学, 医学(系)研究科(研究院), 助教 (40379186)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 成長障害 / 軟骨細胞 / ダウン症候群

Outline of Final Research Achievements

Down syndrome (DS) is the most common chromosomal aneuploidy, which is caused by the trisomy of chromosome 21. Among their various medical symptom, DS patients show impairment in the growth. To analyze the mechanism of this growth impairment in DS, we generated DS-specific human induced pluripotent stem cells (iPSCs) from the cord blood using Sendaivirus vector, and differentiated them to chondrocyte. Although chondrocyte was successfully differentiated from human iPSC, its percentage was not sufficient yet. On the other hand, fibroblasts derived from not only DS patients but also 13, 18 trisomy patients showed low proliferation rate and premature senescence. The premature senescence was accompanied by accelerated RNA / protein synthesis, followed by increased oxidative stress. This trisomy-induced stress can be a major cause of growth impairment in DS.

Free Research Field

胎児・新生児医学