| Project/Area Number |
23591373
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TOJO Arinobu 東京大学, 医科学研究所, 教授 (00211681)
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| Co-Investigator(Renkei-kenkyūsha) |
KOBAYASHI Seiichiro 東京大学医科学研究所, 分子療法分野, 助教 (70376622)
IZAWA Kiyoko 東京大学医科学研究所, 分子療法分野, 特任研究員 (20534415)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | iPS細胞 / 骨髄異形成症候群（MDS） / 初期化因子 / レンチウイルスベクター / センダイウイルスベクター / CD34+細胞 / 骨髄異形成症候群 / CD34陽性細胞 / 細胞初期化 / 遺伝子変異 / MDS / レンチウイルス / Cre/loxP |
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| Research Abstract |
Lentiviral vectors expressing 4 reprogramming factors (Oct4, Sox3, Klf4 and c-Myc) driven by constitutive (EF1a) or inducible (Tet-on) promoter were newly prepared. We tried to reprogram CD34+ cells from 5 patients with MDS (RCMD 3, RARS 1, and MDS/MPD 1) as well as 1 patient with CML-CP by infection with either lentiviral vector. In each case, a number of cell mass resembling iPSC colony appeared over the MEF layer within 3 weeks of culture, but, unfortunately, none of these iPSC-like colonies developed stable cell lines. Then, we took alternative method using a Sendai virus that does not integrate into the host genome. As a result, a patient-derived iPSCs were successfully established from a male patient with RCMD at the very end of the research periods. Since the patient's bone marrow cells revealed normal karyotype, comparative genetic examination between the patient's granulocytes (MDS clone), T cells (normal clone) and iPSCs are required to identify the true origin of iPSCs.
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