Project/Area Number |
23689017
|
Research Category |
Grant-in-Aid for Young Scientists (A)
|
Allocation Type | Single-year Grants |
Research Field |
General medical chemistry
|
Research Institution | Keio University |
Principal Investigator |
OKADA Yohei 慶應義塾大学, 医学部, 訪問准教授 (30383714)
|
Project Period (FY) |
2011-11-18 – 2014-03-31
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
Fiscal Year 2013: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2012: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
|
Keywords | ヒトiPS細胞 / 品質評価 / 神経分化 / 造腫瘍性 |
Research Abstract |
Human-induced pluripotent stem cells (hiPSCs) hold great promise for regenerative medicine. Despite the importance in evaluating their quality for future cell therapy, there are no precise analyses for assessing abnormal differentiation and tumorigenicity. We demonstrated that pre-evaluated hiPSC clones, established by retroviruses or integration-free episomal vectors, may exhibit glioma-like tumor formation by the transplantation of hiPSC-derived neural stem/progenitor cells into NOD/SCID mice. Notably, the tumorigenicities were closely associated with incomplete reprogramming of hiPSCs, revealed by the expressions of newly identified human embryonic stem cell signature genes or DNA repair genes. This incomplete reprogramming resulted in genomic instability not in an undifferentiated state, but during neural differentiation. Moreover, cluster of DNA repair genes may provide a useful "scorecard" for easy and quick evaluation of the incomplete reprogramming of hiPSCs.
|