Hematopoietic stem cell potential is propagated by human pluripotent stem cell-derived endothelial stroma

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659496
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: Kyoto University
• Principal Investigator: NAKAHATA Tatsutoshi 京都大学, iPS細胞研究所, 教授 (20110744)
• Co-Investigator(Renkei-kenkyūsha): NIWA Akira 京都大学, ips細胞研究所, 助教 (20546999) ; OSHIMA Kohichi 京都大学, ips細胞研究所, 研究員 (60525377)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: ES細胞 / iPS細胞 / 造血幹細胞 / ストロマ細胞 / ニッチ

Research Abstract

Elucidating the mechanism of homeostasis in hematopoietic system and developing the culture to expand hematopoietic stem cells are of great interest in medical scientific fields. We developed the method to effectively and robustly induce VE-Cadherin+ endothelial stroma cells from human pluripotent stem cells. Those stromal cells can increase CFU in cord blood CD34+ hematopoietic stem/progenitor fraction by two to three times. Moreover, serial transplantation studies with NOG mice indicated that two-week co-culture can double the Scid-repopulating cells.

Research Products

• [Journal Article] Genetic correction of 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 M. K., Matsubara K., Adachi S., Kobayashi M., Nakahata T., Heike T.
  • Journal Title: Haematologica Volume: 99(1) Pages: 19-27
  • DOI: 10.3324/haemato1.2013.083873
• [Journal Article] Appropriate dose modification in induction therapy is essential for the treatment of infants with acute myeloid leukemia : a report from the JapanesePediatric Leukemia/Lymphoma Study Group (2013)
  • Author(s): Tomizawa D., Tawa A., Watanabe T., Saito A. M., Kudo K., Taga T., Iwamoto S., Shimada A., Terui K., Moritake H., Kinoshita A., Takahashi H., Nakayama H., Kiyokawa N., Isoyama K., Mizutani S., Hara J., Horibe K., Nakahata T., Souichi Adachi S.
  • Journal Title: Int. Hematol Volume: 98(5) Pages: 578-588
  • DOI: 10.1007/s12185-013-1429-2
• [Journal Article] for the Japan Society for Hematopoietic Cell Transplantation, Halter J., Schmitz N., Niederwieser D., Gratwohl A. PBSC collection from family donors in Japan : a prospective survey (2013)
  • Author(s): Kodera Y., Yamamoto K., Harada M., Morishima Y, Dohy H, Asano S, Ikeda Y., Nakahata T., Imamura M., Kawa K., Kato S., Tanimoto M., Kanda Y., Tanosaki R., Shiobara S., Kim SW., Nagafuji K., Hino M., Miyamura K.,Suzuki R., Hama j ima N., Fukushima M., Tamakoshi A.
  • Journal Title: Bone Marrow Transplant
  • DOI: 10.1038/bmt
• [Journal Article] Robust and highly-efficient differentiation of functional monocytic cells from human pluripotent stem cells under serum- and feeder cell- free conditions (2013)
  • Author(s): Yanagimachi M. D., Niwa A., Tanaka T., Ozaki F., Nishimoto S., Murata Y., Yasumi T., Ito J., Tomida S., Oshima K., Asaka I., Goto H., Heike T., Nakahata T., Saito M.K.
  • Journal Title: PLoS ONE Volume: 8 (4) Pages: e59243
  • DOI: 10.1371/journal.pone.0059243
• [Journal Article] Clonal selection in xenografted TAM recapitulates the evolutionary process of myeloid leukemia in Down syndrome (2013)
  • Author(s): Saida S., Watanabe K. I., Sato-Otsubo A., Terui K., Yoshida K., Okuno Y., Toki T., Wang R., Shiraishi Y., Miyano S., Kato I., Morishima T., Fujino H., Umeda K., Hiramatsu H., Adachi S., Ito E., Ogawa S., Ito M., Nakahata T., Heike T.
  • Journal Title: Blood Volume: 121(20 Pages: 4377-4387
  • DOI: 10.1182/blood-2012-12-474387
• [Journal Article] Recipient seropositivity for adenovirus type 11 is a highly predictive factor for the development of AdV11-inducedhemorrhagic cystitis after allogeneic hematopoietic SCT (2013)
  • Author(s): Nakazawa Y., Saito S., Yanagisawa R., Suzuki T., Toshiro Ito T., Ishida F., Muramatsu H., Matsumoto K., Kato K., Ishida H., Umeda K., Souichi Adachi S., Nakahata T., Koike K.
  • Journal Title: Bone Marrow Transplant Volume: 48 Pages: 737-739
  • DOI: 10.1038/bmt.2012.206
• [Journal Article] 疾患特異的ips細胞 (2013)
  • Author(s): 斎藤潤、中畑龍俊
  • Journal Title: 再生医療 Volume: 12(1) Pages: 19-29
• [Journal Article] The CD40-CD40L axis and INF-g play critical roles in Langerhans giant cell formation (2012)
  • Author(s): Sakai H., Okafuji I., Nishikomori R., Abe J., Izawa K., Kambe N., Yasumi T., Nakahata T., Heike T.
  • Journal Title: Int. Immunol Volume: 24(1) Pages: 5-15
  • DOI: 10.1093/intimm/dxr088
• [Journal Article] Detection of base substitution-type somatic mosaicism of the NLRP3 gene with >99.9% statistical confidence by massively parallel sequencing (2012)
  • Author(s): IzawaK., Hijikata A., Tanaka N., Kawai T., Saito M. K., Goldbach-Mansky R., Aksentijevich I., Yasumi T., Nakahata T., Heike T., Nishikomori R., Ohara0.
  • Journal Title: DNA Res Volume: 19(2) Pages: 143-152
  • DOI: 10.1093/dnares/dsr047
• [Journal Article] Frequent somatic mosaicism of NEMO in T cells of patients with X-linked anhidrotic ectodermal dysplasia and immunodeficiency (2012)
  • Author(s): Kawai T., Nishikomori R., Izawa K., Murata Y., Tanaka N., Sakai H., Saito M., Yasumi T., Takaoka Y., Nakahata T., Mizukami T., Nunoi H., Kiyohara Y., Yoden A., Mutara T., Sasaki S., Ito E., Akutagawa H., Kawai T., Imai C., Okada S., Kobayashi M., Heike T.
  • Journal Title: Blood Volume: 119(23) Pages: 5458-66
  • DOI: 10.1182/blood-2011-05-354167
• [Journal Article] Dominant-negative STAT1 SH2 domain mutations in unrelated patients with Mendelian susceptibility to mycobacterial disease (2012)
  • Author(s): Tsumura M., Okada S., Sakai H., Yasunaga S., Ohtsubo M., Murata T., Obata H., Yasumi T., Kong X., Abhyankar A., Heike T., Nakahata T., Nishikomori R., Al-Muhsen S., Boisson-Dupuis S., Casanova J., AlZahrani M., Shehri MA., ElGhazali G., Takihara Y., Kobayashi M.
  • Journal Title: Human Mutation Volume: 33(9) Pages: 1377-87
  • DOI: 10.1002/humu.22113
• [Journal Article] Outcome of children with Refractory Anaemia with Excess of Blast (RAEB) and RAEB in Transformation (RAEB-T) in the Japanese MDS99 study (2012)
  • Author(s): Kikuchi A., Hasegawa D., Ohtsuka Y., Hamamoto K., Ko j ima S., Okamura J., Nakahata T., Manabe A.
  • Journal Title: Brit. J. Haematol Volume: 158(5) Pages: 657-661
  • DOI: 10.1111/j.1365-2141.2012.09210.x
• [Journal Article] Induced pluripotent stem cells from CINCA syndrome patients as a model for dissecting somatic mosaicism and drug discovery (2012)
  • Author(s): Tanaka T., Takahashi K., Yamane M., Tomida S., Nakamura S., Oshima K., Niwa A., Nishikomori R., Kambe N., Hara H., Mitsuyama M., Morone N., Heuse J. E., Yamamoto T., Watanabe A., Sato-Otsubo A., Ozawa S., Asaka I., Heike T., Yamanaka S., Nakahata T., Saito M.K.
  • Journal Title: Blood Volume: 120(6) Pages: 1299-308
  • DOI: 10.1182/blood-2012-03-417881
• [Journal Article] Multiple reversions of an IL2RG mutation restore combined immunodeficiency patient (2012)
  • Author(s): Kawai T., Saito M., Nishikomori R., Yasumi T., Izawa K., Murakami T., Okamoto N., Mori Y., Nakagawa N., Imai K., Nonoyama S., Wada T., Yatie A., Oomori K., Nakahata T., Heike T.
  • Journal Title: J. Clin. Immunol Volume: 32(4) Pages: 690-7
  • DOI: 10.1007/s10875-012-9684-1
• [Journal Article] 白血病治療の進歩と今後の展望.日本小児 (2012)
  • Author(s): 中畑龍俊
  • Journal Title: 血液・がん学会雑誌 Volume: 第49巻1・2号 Pages: 11-15
• [Journal Article] 幹細胞増幅、第10章内科疾患と再生医療 (2012)
  • Author(s): 中畑龍俊、丹羽明
  • Journal Title: カラー版内科学、門脇孝、永井良三(総編集) Pages: 447-450
• [Journal Article] Clinical characteristics of 15 children with juvenile myelomonocytic 1 leukemia who developed blast crisis : MDS Committee of Japanese Society of Pediatric Hematology/Oncology (JSPHO)
  • Author(s): Honda Y., Tsuchida M., , Zaike Y., Masunaga A., Yoshimi A., Kojima S., Ito M., Kikuchi A., Nakahata T., Manabe A.
  • Journal Title: Brit. J. Haematol Volume: (In press)
• [Journal Article] The clinical utility of genetic testing for t(8;16) (p11;p13) in congenital acute myeloid leukemia
  • Author(s): Daifu T., Kato I., Kozuki K., Umeda K., Hiramatsu H., Watanabe K., Kamiya I., Taki T., Nakahata T., Heike T., Adachi S.
  • Journal Title: J. Pediatr. Hematol/Onc Volume: (In press)
• [Journal Article] Excess reduction of anthracyclines results in inferior event-free survival in core binding factor acute myeloid leukemia in children; a report from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG)
  • Author(s): Tomizawa D., Tawa A., Watanabe T., Saito A. M., Kudo K., Taga T., Iwamoto S., Shimada A., Terui K., Moritake H., Kinoshita A., Takahashi H., Nakayama H., Koh K., Kigasawa H., Kosaka Y., Miyachi H., Horibe K., Nakahata T., Adachi S.
  • Journal Title: Leukemia
  • DOI: 10.1038/leu.2013.153
• [Presentation] ips細胞の臨床応用 (2013)
  • Author(s): 中畑龍俊
  • Organizer: 第55回日本小児」血液・がん学会学術集会
  • Place of Presentation: ヒルトン福岡シーホーク
  • Year and Date: 20131129-1201
• [Presentation] Xenograft model of TAM reveals the evolutionary process of myeloid leukemia in Down syndrome (2013)
  • Author(s): Saida S., Watanabe K., Sato-Otsubo A., Terui K., Yoshida K., Okuno Y., Toki T., Wang R., Shiraishi Y., Miyano S., Kato I., Umeda K., Hiramatsu H., Fu j ino H., Adachi S., Nakahata T., Ito E., Ogawa S., Heike T.
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: 札幌市教育分化会館(一般口演)
  • Year and Date: 20131011-13
• [Presentation] Mesodermal development from reprogrammed Fanconi anemia cells is affected by ALDH2 enzymatic activity (2013)
  • Author(s): Suzuki N., Hira A., Niwa A., Matsuo K., Takata M., Yabe M., Nakahata T., Saito M.
  • Organizer: 11th Annual Meeting of international Society for Stem Cell Research (ISSCR)
  • Place of Presentation: Boston, MA, USA
  • Year and Date: 20130712-15
• [Presentation] ips細胞の小児医療への応用 (2013)
  • Author(s): 中畑龍俊
  • Organizer: 第38回東日本小児科学会
  • Place of Presentation: 大宮ソニックシティ
  • Year and Date: 2013-11-23
• [Presentation] ips細胞を活用した医療の可能性と倫理 (2013)
  • Author(s): 中畑龍俊
  • Organizer: 第10回STSフォーラム「科学技術が拓く人間の未来」公開シンポジウム
  • Place of Presentation: 京都商工会議所ビル講堂
  • Year and Date: 2013-10-05
• [Presentation] さい帯血造血幹細胞発見秘話とips細胞ストックの月齊帯 (2013)
  • Author(s): 中畑龍俊
  • Organizer: 血活用の未来像.さい帯血移植1万例突破記念事業「さらなる飛躍へのステップ」記念講演会
  • Place of Presentation: TKP田町カンファレンスセンター
  • Year and Date: 2013-09-28
• [Presentation] ips細胞研究が切り開く未来の医療 (2013)
  • Author(s): 中畑龍俊
  • Organizer: 日本学術会議公開学術講演会「未来社会を築く生命科学と医療のフロンティア」
  • Place of Presentation: 京都大学薬学部記念講堂
  • Year and Date: 2013-08-03
• [Presentation] Immunosuppressive therapy with antithymocyte globulin and Cyclosporine for fulminant aplastic anemia (2012)
  • Author(s): Yagasaki H., Watanabe K., Kudo K., Tsuchida M., Shichino H., Morimoto A., Kobayashi R., Yabe H., Kikuchi A., Ohga S., Ito E., Ohara A., Nakahata N., Kojima S.
  • Organizer: 54th Annual Meeting of the AMERICAN SOCIETY of HEMATOLOGY
  • Place of Presentation: Atlanta
  • Year and Date: 20121208-11
• [Presentation] ips細胞研究の進展 (2012)
  • Author(s): 中畑龍俊
  • Organizer: 第59回日本臨床検査医学会学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 20121129-1202
  • Invited
• [Presentation] 小児患者におけるips細胞の応用 (2012)
  • Author(s): 中畑龍俊
  • Organizer: 第49回日本小児アレルギー学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 20120915-16
• [Presentation] Differentiation of monocytic lineage cells from human iPS cells by using a serum and feeder free culture method (2012)
  • Author(s): Yanagimachi M., Niwa A., Tanaka T. Oshima K., Saito M., Nakahata T.
  • Organizer: 10◎<th>◎ Annual Meeting of International Society for Stem Cell Research (ISSCR)
  • Place of Presentation: Pacifico Yokohama, Japan
  • Year and Date: 20120613-16
• [Presentation] Human ESC/IPSC-Derived mesenchymal stroma can support hematopoietic progenitors (2012)
  • Author(s): Niwa A., Saito M., Oshima K., Yanagimachi M., Tanaka T., Kato I., Nakahata T.
  • Organizer: 10◎<th>◎ Annual Meeting of International Society for Stem Cell Research (ISSCR)
  • Place of Presentation: Pacifico Yokohama, Japan
  • Year and Date: 20120613-16
• [Presentation] Induced pluripotent stem cell model of severe congenital neutropenia with HAX1 gene deficiency (2012)
  • Author(s): Morishima T., Watanabe K., Niwa A., Tanaka T, Saida S, Kato I, Umeda K, Hiramatsu H., Matsubara K., Adachi S., Nakahata T., Heike T.
  • Organizer: 10th Annual Meeting of International Society for Stem Cell Research (ISSCR)
  • Place of Presentation: Pacifico Yokohama, Japan
  • Year and Date: 20120613-16
• [Presentation] Induced pluripotent stem cells from CINCA syndrome patients as a model for dissecting somatic mosaicism and drug discovery (2012)
  • Author(s): Tanaka T., Saito M. K.., Takahashi K., Yamanaka S., Nakahata T.
  • Organizer: 10th Annual Meeting of International Society for Stem Cell Research (ISSCR)
  • Place of Presentation: Pacifico Yokohama, Japan
  • Year and Date: 20120613-16
• [Presentation] 次世代シーケンサーによるNLRP3体制モザイクの診断 (2012)
  • Author(s): 井澤和司、土方敦司、西小森隆太、小原収、田中尚子、河合朋樹、八角高裕、斎藤潤、中畑龍俊、平家俊男
  • Organizer: 第115回日本小児科学会学術集会
  • Place of Presentation: 福岡国際会議場福岡市(口演)
  • Year and Date: 20120420-22
• [Presentation] ips細胞研究の今、その可能性と将来展望 (2012)
  • Author(s): 中畑龍俊
  • Organizer: 第115回日本小児科学会学術集会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 20120420-22
• [Remarks] 中畑研究室ホームページ:
  • URL: http://www.cira.kyoto-u.ac.jp/nakahata