| Project/Area Number |
25670194
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Experimental pathology
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| Research Institution | Kagoshima University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
MITSUI Kaoru 鹿児島大学, 医歯学域医学系, 講師 (40324975)
IRIE Rie 鹿児島大学, 医歯学域医学系, 助教 (90381178)
IJICHI Nobuhiro 鹿児島大学, 医歯学域医学系, 助教 (80380624)
WAN Yu-chin 鹿児島大学, 医歯学総合研究科, 分担研究員 (20505143)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 再生医学 / iPS細胞 / 遺伝子治療 / ウイルスベクター / 腫瘍溶解性ウイルス / サバイビン / 腫瘍化 / ES細胞 |
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| Outline of Final Research Achievements |
Incomplete abolition of tumorigenicity creates potential safety concerns in clinical human pluripotent stem cells (hPSCs)-based regenerative medicine. We found that conditionally replicating adenoviruses that specifically target cancers using multiple factors (m-CRAs), originally developed as anticancer drugs, may also be useful as novel antitumorigenic agents in hPSC-based therapy. The survivin promoter was more active in undifferentiated hPSCs than the telomerase reverse transcriptase (TERT) promoter, whereas both promoters were minimally active in differentiated ones. Accordingly, survivin-responsive m-CRA (Surv.m-CRA) killed only undifferentiated hPSCs, but not undifferentiated ones, more efficiently than TERT-responsive m-CRAs (Tert.m-CRA). Pre-infection of hPSCs with Surv.m-CRA or Tert.m-CRA abolished in vivo teratoma formation following hPSC implantation into mice. Thus, m-CRAs may be novel antitumorigenic agents in hPSC-based regenerative medicine.
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