Induction and expansion of PSC-derived HSCs by manipulating culture microenvironment
Project/Area Number |
26670498
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Pediatrics
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Research Institution | Kyoto University |
Principal Investigator |
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Co-Investigator(Renkei-kenkyūsha) |
NIWA Akira 京都大学, iPS細胞研究所, 助教 (20546999)
Osawa Mitsujiro 京都大学, iPS細胞研究所, 助教 (70546770)
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Project Period (FY) |
2014-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | 造血幹細胞 / ES/iPS細胞 / 移植・再生医療 / 臨床応用 / 細胞内代謝 / ストロマ細胞 / ニッチ / ES/iPS細胞 |
Outline of Final Research Achievements |
Developing the way of hematopoietic stem cell (HSC) expansion or de novo stem cell induction has been of great interest in medical scientific fields. We cleared that pluripotent stem cell (PSC)-derived VE-Cadherin+ endothelial cells function as stromal microenvironment to induce PSC-derived HSC-like cells; they showed serial colony forming potential in vivo and were observed engrafted in NOG mice as long as twelve weeks. Moreover, a small molecule cocktail containing GSK3 and AHR pathway inhibitors successfully expanded them as high as six times in vitro, and increased the chimerism in vivo.
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Report
(3 results)
Research Products
(46 results)
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[Journal Article] Specific Antileukemic Activity of PD0332991, a CDK4/6 Inhibitor, against Philadelphia Chromosome-Positive Lymphoid Leukemia.2016
Author(s)
Nemoto A, Saida S, Kato I, Kikuchi J, Furukawa Y, Maeda Y, Akahane K, Honna-Oshiro H, Goi K, Kagami K, Kimura S, Sato Y, Okabe S, Niwa A, Watanabe K, Nakahata T, Heike T, Sugita K, Inukai T.
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Journal Title
Mol Cancer Ther.
Volume: 15
Issue: 1
Pages: 94-105
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] High event-free survival rate with minimum-dose-anthracycline treatment in childhood acute promyelocytic leukaemia: a nationwide prospective study by the Japanese Paediatric Leukaemia/Lymphoma Study Group.2016
Author(s)
Takahashi H, Watanabe T, Kinoshita A, Yuza Y, Moritake H, Terui K, Iwamoto S, Nakayama H, Shimada A, Kudo K, Taki T, Yabe M, Matsushita H, Yamashita Y, Koike K, Ogawa A, Kosaka Y, Tomizawa D, Taga T, Saito AM, Horibe K, Nakahata T, Miyachi H, Tawa A, Adachi S.
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Journal Title
Br J Haematol.
Volume: 印刷中
Issue: 3
Pages: 437-443
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Establishment of isogenic iPSCs from an individual with SCN1A mutation mosaicism as a model for investigating neurocognitive impairment in Dravet syndrome.2016
Author(s)
Maeda H, Chiyonobu T, Yoshida M, Yamashita S, Zuiki M, Kidowaki S, Isoda K, Yamakawa K, Morimoto M, Nakahata T, Saito MK, Hosoi H.
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Journal Title
J Hum Genet.
Volume: 印刷中
Issue: 6
Pages: 565-569
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] In vitro expansion of CD34(+)CD38(-) cells under stimulation with hematopoietic growth factors on AGM-S3 cells in juvenile myelomonocytic leukemia.2015
Author(s)
Sakashita K, Kato I, Daifu T, Saida S, Hiramatsu H, Nishinaka Y, Ebihara Y, Ma F, Matsuda K, Saito S, Hirabayashi K, Kurata T, Uyen Lt, Nakazawa Y, Tsuji K, Heike T, Nakahata T, Koike K.
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Journal Title
Leukemia.
Volume: 29(3)
Issue: 3
Pages: 606-14
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Enhanced chondrogenesis of induced pluripotent stem cells from patients with neonatal-onset multisystem inflammatory disease occurs via the caspase 1-independent cAMP/protein kinase A/CREB pathway2015
Author(s)
Yokoyama, K. Ikeya, M. Umeda, K. Oda, H. Nodomi, S. Nasu, A. Matsumoto, Y. Izawa, K. Horigome, K. Kusaka, T. Tanaka, T. Saito, M. K. Yasumi, T. Nishikomori, R. Ohara, O. Nakayama, N. Nakahata, T. Heike, T. Toguchida, J.
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Journal Title
Arthritis Rheumatol
Volume: 67
Issue: 1
Pages: 302-314
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Pluripotent cell models of Fanconi anemia identify the early pathological defect in human hemoangiogenic progenitors.2015
Author(s)
Suzuki NM, Niwa A, Yabe M, Hira A, Okada C, Amano N, Watanabe A, Watanabe K, Heike T, Takata M, Nakahata T, Saito MK
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Journal Title
Stem Cells Transl Med
Volume: 4
Issue: 4
Pages: 333-338
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Modeling the early phenotype at the euromuscular junction of spinal muscular atrophy using patient-derived iPSCs.2015
Author(s)
Yoshida, M., Kitaoka, S., Egawa N., Yamane M., Ikeda R., Tsukita K., Amano N., Watanabe A., Morimoto, M., Takahashi J., Hosoi H., Nakahatan, T., Inoue, H.,Saito, Megumu K.
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Journal Title
Stem Cell Reports
Volume: 4
Issue: 4
Pages: 1-8
DOI
Related Report
Peer Reviewed
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[Journal Article] The clinical utility of genetic testing for t(8;16)(p11;p13) in congenital acute myeloid leukemia.2014
Author(s)
Daifu T., Kato I., Kozuki K., Umeda K., Hiramatsu H., Watanabe K., Kamiya I., Taki T., Nakahata T., Heike T., Adachi S.
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Journal Title
J Pediatr Hematol Oncol.
Volume: 36
Issue: 5
Pages: e325-e327
DOI
Related Report
Peer Reviewed
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[Journal Article] HAX1 in induced pluripotent stem cells from a patient with severe congenital neutropenia improves defective granulopoiesis.2014
Author(s)
Morishima T, Watanabe K, Niwa A, Hirai H, Saida S, Tanaka T, Kato I, Umeda K, Hiramatsu H, Saito MK, Matsubara K, Adachi S, Kobayashi M, Nakahata T, Heike T
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Journal Title
Haematologica
Volume: 99(1)
Issue: 1
Pages: 19-27
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Peripheral blood lymphocyte telomere length as a predictor of response to immunosuppressive therapy in childhood aplastic anemia.2014
Author(s)
Sakaguchi H, Nishio N, Hama A, Kawashima N, Wang X, Narita A, Doisaki S, Xu Y, Muramatsu H, Yoshida N, Takahashi Y, Kudo K, Moritake H, Nakamura K, Kobayashi R, Ito E, Yabe H, Ohga S, Ohara A, Kojima S; Japan Childhood Aplastic Anemia Study Group.
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Journal Title
Haematologica
Volume: 99
Issue: 8
Pages: 1312-1316
DOI
Related Report
Peer Reviewed
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[Journal Article] Clinical characteristics and treatment outcome in 65 cases with refractory cytopenia of childhood defined according to the WHO 2008 classification.2014
Author(s)
Hasegawa D, Chen X, Hirabayashi S, Ishida Y, Watanabe S, Zaike Y, Tsuchida M, Masunaga A, Yoshimi A, Hama A, Kojima S, Ito M, Nakahata T, Manabe A.
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Journal Title
Br J Haematol.
Volume: 166
Issue: 5
Pages: 758-66
DOI
Related Report
Peer Reviewed
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[Journal Article] Derivation of mesenchymal stromal cells from pluripotent stem cells through a neural crest lineage using small molecule compounds with defined media.2014
Author(s)
Fukuta M, Nakai Y, Kirino K, Nakagawa M, Sekiguchi K, Nagata S, Matsumoto Y, Yamamoto T, Umeda K, Heike T, Okumura N, Koizumi N, Sato T, Nakahata T, Saito M, Otsuka T, Kinoshita S, Ueno M, Ikeya M, Toguchida J.
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Journal Title
PLOS ONE
Volume: 9
Issue: 12
Pages: e112291-e112291
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Risk-Oriented Therapy for Myeloid Leukemia of Down Syndrome: A Nationwide Prospective Study By the Japanese Pediatric Leukemia / Lymphoma Study Group (JPLSG).2014
Author(s)
Taga T, Watanabe T , Kudo K, Tomizawa D, Terui K, Moritake H, Kinoshita A, Iwamoto S, Nakayama H, Takahashi H, Shimada A, Taki T, Toki T, Ito E, Goto H, Koh K, A.M. Saito, Horibe K, Nakahata T, Tawa A, Adachi S
Organizer
56th Annual Meeting of the AMERICAN SOCIETY of HEMATOLOGY
Place of Presentation
Mascone Convention Center(San Francisco,USA)
Year and Date
2014-12-06 – 2014-12-09
Related Report
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[Presentation] High Event-Free Survival Rate with Minimum-Dose-Anthracycline Treatment in Childhood Acute Promyelocytic Leukemia: A Nationwide Prospective Study By the Japanese Pediatric Leukemia / Lymphoma Study Group (JPLSG).2014
Author(s)
Takahashi H, Watanabe T, Kinoshita A, Y, Moritake H, Terui K, Iwamoto S, Nakayama H, Shimada A, Kudo K, Taki T, Yabe M, Matsushita H, Yamashita Y, Koike K, Ogawa A, Kosaka Y, Tomizawa D, Taga T, A.K.Saito, Horibe K, Nakahata T, Miyachi H, Tawa A,Adachi S
Organizer
56th Annual Meeting of the AMERICAN SOCIETY of HEMATOLOGY
Place of Presentation
Mascone Convention Center(San Francisco,USA)
Year and Date
2014-12-06 – 2014-12-09
Related Report
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[Presentation] Hematopoietic Stem Cell Transplantation for Patients with Refractory Cytopenia of Childhood.2014
Author(s)
Daisuke Hasegawa , Shinsuke Hirabayashi , Shizuka Watanabe, Yuji Zaike , Masahiro Tsuchida,Atsuko Masunaga, Ayami Yoshimi, Asahito Hama, Seiji Kojima, Masafumi Ito, Tatsutoshi Nakahata, Atsushi Manabe
Organizer
56th Annual Meeting of the AMERICAN SOCIETY of HEMATOLOGY
Place of Presentation
Mascone Convention Center(San Francisco,USA)
Year and Date
2014-12-06 – 2014-12-09
Related Report
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[Presentation] Modeling chronic myelomonocytic leukemia through patient-derived induced pluripotent stem cells.2014
Author(s)
Kazuki Taoka, Syunya Arai, Masataka Hosai, Fimihiko Nakamura, Masashi Miyauchi, Sho Yamazaki, Akira Honda, Keisuke Kataoka, Keiki Kumano, Akihide Yoshimi, Koji Eto, Hiromitsu Nakauchi, Tatsutoshi Nakahata, Mineo Kurokawa
Organizer
第76回日本血液学会学術集会
Place of Presentation
大阪国際会議場
Year and Date
2014-10-31
Related Report
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[Presentation] Mechanisms of CDK4/6 inhibitor hypersensitivity in Ph+ lymphoid leukemia.2014
Author(s)
Atsushi Nemoto, Takeshi Inukai, Satoshi Saida, Itaru Kato, Toshio Heike, Tatsutoshi Nakahata, Jiro Kikuchi, Yusuke Furukawa, Kumiko Goi, Kanako Uno, Atsushi Watanabe, Sinpei Somazu, Meixian Huang, Keiko Kagami, Kanji Sugita
Organizer
第76回日本血液学会学術集会
Place of Presentation
大阪国際会議場
Year and Date
2014-10-31
Related Report
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