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Cotransplantation with MSCs improves engraftment of HSCs after autologous intra-bone marrow transplantation in nonhuman primates

Research Project

Project/Area Number 21790922
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionJichi Medical University

Principal Investigator

MASUDA Shigeo  Jichi Medical University, 医学部, 講師 (10396749)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords霊長類 / サル / 造血幹細胞 / 間葉系幹細胞 / 骨髄内移植 / ニッチ / 生着 / 造血幹細胞ニッチ / 骨芽細胞性ニッチ
Research Abstract

Hematopoietic stem cells (HSCs) reside in the osteoblastic niche, which consists of osteoblasts derived from mesenchymal stem cells (MSCs). Here, using nonhuman primates, we investigated the effects of cotransplantation with MSCs on the engraftment of genetically marked CD34^+ cells after autologous intra-bone marrow transplantation (iBMT). In three cynomolgus monkeys, CD34^+ cells transplanted with MSCs engrafted 4.4-, 6.0-, and 1.6-times more efficiently than CD34^+ cells alone, as assessed by bone marrow (BM) colony PCR. In addition, virtually all of the marked cells detected in the peripheral blood (PB) were derived from the cotransplantation aliquots. Notably, colony-forming units (CFUs) derived from the cotransplantation aliquots were frequently detected in BM, distant from the injection site. Thus, cotransplantation with MSCs would improve the efficacy of transplantation of gene-modified HSCs in primates, with enhanced engraftment in BM as well as increased chimerism in PB through migration and homing.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (53 results)

All 2011 2010 2009 2008 Other

All Journal Article (21 results) (of which Peer Reviewed: 18 results) Presentation (30 results) Remarks (2 results)

  • [Journal Article] Induced pluripotent stem cells in long-QT syndrome.2011

    • Author(s)
      Masuda S, Hanazono Y.
    • Journal Title

      N Engl J Med. 364(2)

      Pages: 181-182

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Leukemic stem cell gene expression signature and clinical outcomes in acute myeloid leukemia.2011

    • Author(s)
      Masuda S.
    • Journal Title

      JAMA. 305(11)

      Pages: 1094-1095

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ex vivo expansion of human HSCs with Sendai virus vector expressing HoxB4 assessed by sheep in utero transplantation.2011

    • Author(s)
      Abe T, Masuda S, Ban H, Hayashi S, Ueda Y, Inoue M, Hasegawa M, Nagao Y, Hanazono Y.
    • Journal Title

      Exp Hematol. 39(1)

      Pages: 47-54

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Induced pluripotent stem cells in long-QT syndrome.2011

    • Author(s)
      Masuda S, Hanazono
    • Journal Title

      N Engl J Med.

      Volume: 364(2) Pages: 181-182

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NK-cell and B-cell deficiency with a thymic mass.2011

    • Author(s)
      Masuda S
    • Journal Title

      N Engl J Med.

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Leukemic stem cell gene expression signature and clinical outcomes in acute myeloid leukemia.2011

    • Author(s)
      Masuda S
    • Journal Title

      JAMA.

      Volume: 305(11) Pages: 1094-1095

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ex vivo expansion of human HSCs with Sendai virus vector expressing HoxB4 assessed by sheep in utero transplantation.2011

    • Author(s)
      Abe T, Masuda S, et al.
    • Journal Title

      Exp Hematol.

      Volume: 39(1) Pages: 47-54

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Busulfan conditioning in sheep in utero transplantation confers engraftment potential on human hematopoietic stem cells as efficiently as HoxB4 transduction.2010

    • Author(s)
      Masuda S, Abe T, Hayashi S, Tanaka Y, Ban H, Inoue M, Hasegawa M, Nagao Y, Hanazono Y.
    • Journal Title

      Blood. 116(22)

    • Related Report
      2010 Final Research Report
  • [Journal Article] Intravascular route is not superior to an intraperitoneal route for in utero transplantation of human hematopoietic stem cells and engraftment in sheep.2010

    • Author(s)
      Tanaka Y, Masuda S, Abe T, Hayashi S, Kitano Y, Nagao Y, Hanazono Y.
    • Journal Title

      Transplantation. 90(4)

      Pages: 462-463

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Busulfan conditioning in sheep in utero transplantation confers engraftment potential on human hematopoietic stem cells as efficiently as HoxB4 transduction.2010

    • Author(s)
      Masuda S, Abe T, et al.
    • Journal Title

      Blood.

      Volume: 116(22)

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Intravascular route is not superior to an intraperitoneal route for inutero transplantation of human hematopoietic stem cells and engraftment in sheep.2010

    • Author(s)
      Tanaka Y, Masuda S, et al.
    • Journal Title

      Transplantation.

      Volume: 90(4) Pages: 462-463

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cotransplantation with MSCs improves engraftment of HSCs after autologous intra-bone marrow transplantation in nonhuman primates.2009

    • Author(s)
      Masuda S, Ageyama N, Shibata H, Obara Y, Ikeda T, Takeuchi K, Ueda Y, Ozawa K, Hanazono Y.
    • Journal Title

      Exp Hematol. 37(10)

      Pages: 1250-1257

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dual antitumor mechanisms of Notch signaling inhibitor in a T-cell acute lymphoblastic leukemia xenograft model.2009

    • Author(s)
      Masuda S, Kumano K, Suzuki T, Tomita T, Iwatsubo T, Natsugari H, Tojo A, Shibutani M, Mitsumori K, Hanazono Y, Ogawa S, Kurokawa M, Chiba S.
    • Journal Title

      Cancer Sci. 100(12)

      Pages: 2444-2450

    • NAID

      10027198807

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Notch activation induces the generation of functional natural killer cells from human cord blood CD34-positive cells devoid of interleukin-15.2009

    • Author(s)
      Haraguchi K, Suzuki T, Koyama N, Kumano K, Nakahara F, Matsumoto A, Yokoyama Y, Sakata-Yanagimoto M, Masuda S, Takahashi T, Kamijo A, Takahashi K, Takanashi M, Okuyama Y, Yasutomo K, Sakano S, Yagita H, Kurokawa M, Ogawa S, Chiba S.
    • Journal Title

      J Immunol. 182(10)

      Pages: 6168-6178

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] ERas is expressed in primate embryonic stem cells but not related to tumorigenesis.2009

    • Author(s)
      Tanaka Y, Ikeda T, Kishi Y, Masuda S, Shibata H, Takeuchi K, Komura M, Iwanaka T, Muramatsu S, Kondo Y, Takahashi K, Yamanaka S, Hanazono Y.
    • Journal Title

      Cell Transplant. 18(4)

      Pages: 381-389

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cotransplantation with MSCs improves engraftment of HSCs after autologous intra-bone marrow transplantation in nonhuman primates.2009

    • Author(s)
      Masuda S, Ageyama N, et al.
    • Journal Title

      Exp Hematol. 37(10)

      Pages: 1250-1257

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dual antitumor mechanisms of Notch signaling inhibitor in a T-cell acute lymphoblastic leukemia xenograft model.2009

    • Author(s)
      Masuda S, Kumano K, et al.
    • Journal Title

      Cancer Sci. 100(12)

      Pages: 2444-2450

    • NAID

      10027198807

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Safe and efficient expansion of human HSC with Sendai virus vector expressing HoxB4 in fetal sheep.2009

    • Author(s)
      Masuda S, Abe T, et al.
    • Journal Title

      Blood 114(22)

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Notch activation induces the generation of functional natural killer cells from human cord blood CD34-positive cells devoid of interleukin-15.2009

    • Author(s)
      Haraguchi K, Masuda S, et al.
    • Journal Title

      J Immunol. 182(10)

      Pages: 6168-6178

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ERas is expressed in primate embryonic stem cells but not related to tumorigenesis.2009

    • Author(s)
      Tanaka Y, Masuda S, et al.
    • Journal Title

      Cell Transplant. 18(4)

      Pages: 381-389

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NK-cell and B-cell deficiency with a thymic mass.

    • Author(s)
      Masuda S.
    • Journal Title

      N Engl J Med. In press.

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] 造血幹細胞移植における間葉系幹細胞共移植療法の開発(霊長類モデルを用いて)2011

    • Author(s)
      増田茂夫
    • Organizer
      第36回冲中記念成人病研究所研究報告会
    • Place of Presentation
      東京(虎の門病院)
    • Year and Date
      2011-03-05
    • Related Report
      2010 Final Research Report
  • [Presentation] 造血幹細胞移植における間葉系幹細胞共移植療法の開発(霊長類モデルを用いて)2011

    • Author(s)
      増田茂夫
    • Organizer
      第36回沖中記念成人病研究所研究報告会
    • Place of Presentation
      東京(虎の門病院)
    • Year and Date
      2011-03-05
    • Related Report
      2010 Annual Research Report
  • [Presentation] In Utera Transplantation to Busulfan-conditioned Sheep Fetuses Enhances Engraftment of Human Hematopoietic Stem Cells2011

    • Author(s)
      Abe T, Masuda S, et al.
    • Organizer
      Keystone Symposium (Stem Cells in Development)
    • Place of Presentation
      アメリカ合衆国(サンタフェ)
    • Related Report
      2010 Annual Research Report
  • [Presentation] サルおよびブタ線維芽細胞由来のiPS細胞樹立2010

    • Author(s)
      藤城修平、増田茂夫, et al.
    • Organizer
      第9回自治医大シンポジウム
    • Place of Presentation
      栃木(自治医大)
    • Year and Date
      2010-09-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] 大型動物を用いたiPS細胞研究2010

    • Author(s)
      増田茂夫
    • Organizer
      第2回滋賀医科大学サルシンポジウム(招待講演)
    • Place of Presentation
      滋賀(滋賀医科大学)
    • Year and Date
      2010-02-22
    • Related Report
      2010 Final Research Report
  • [Presentation] 大型動物を用いたiPS細胞研究(招待講演)2010

    • Author(s)
      増田茂夫
    • Organizer
      第2回滋賀医科大学サルシンポジウム
    • Place of Presentation
      滋賀(滋賀医科大学)
    • Year and Date
      2010-02-22
    • Related Report
      2009 Annual Research Report
  • [Presentation] Cotransplantation with MSCs improves engraftment of HSCs after autologous intra-bone marrow transplantation in nonhuman primates.2010

    • Author(s)
      増田茂夫
    • Organizer
      第9回日本再生医療学会総会(YIA受賞口演)
    • Place of Presentation
      広島(広島国際会議場)
    • Related Report
      2010 Final Research Report
  • [Presentation] A new-type Sendai virus vector expressing HoxB4 allows safe and efficient expansion of human HSC in a sheep in utero transplant model2010

    • Author(s)
      Masuda S
    • Organizer
      第8回幹細胞シンポジウム
    • Place of Presentation
      兵庫(淡路夢舞台国際会議場)
    • Related Report
      2010 Annual Research Report
  • [Presentation] HoxB4遺伝子の一過性発現によるヒト造血幹細胞のヒツジ体内における生着率の向上2010

    • Author(s)
      阿部朋行、増田茂夫, et al.
    • Organizer
      第57回日本実験動物学会総会
    • Place of Presentation
      京都(京都テルサ)
    • Related Report
      2010 Annual Research Report
  • [Presentation] EX VIVO EXPANSION OF HUMAN HSC WITH GENOTOXICITY-FREE SENDAI VIRUS VECTOR TRANSIENTLY EXPRESSING HOXB4 ASSESSED BY SHEEP IN UTERO TRANSPLANTATION.2010

    • Author(s)
      Masuda S
    • Organizer
      第16回日本遺伝子治療学会学術集会
    • Place of Presentation
      栃木(栃木県総合文化センター)
    • Related Report
      2010 Annual Research Report
  • [Presentation] GENERATION OF INDUCED PLURIPOTENT STEM CELLS FROM MONKEY AND PIG FIBROBLASTS.2010

    • Author(s)
      Fujishiro S, Masuda S, et al.
    • Organizer
      第16回日本遺伝子治療学会学術集会
    • Place of Presentation
      栃木(栃木県総合文化センター)
    • Related Report
      2010 Annual Research Report
  • [Presentation] サルおよびブタ線維芽細胞由来のiPS細胞樹立2010

    • Author(s)
      藤城修平、増田茂夫, et al.
    • Organizer
      第72回日本血液学会総会
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Busulfan Conditioning in Sheep In Utero Transplantation Confers Engraftment Potential on Human Hematopoietic Stem Cells as Efficiently as HoxB4 Transduction.2010

    • Author(s)
      Masuda S
    • Organizer
      第52回米国血液学会総会
    • Place of Presentation
      アメリカ合衆国(オーランド)
    • Related Report
      2010 Annual Research Report
  • [Presentation] サルおよびブタ線維芽細胞由来のiPS細胞樹立2010

    • Author(s)
      藤城修平、増田茂夫, et al.
    • Organizer
      第33回日本分子生物学会年会
    • Place of Presentation
      兵庫(神戸ポートアイランド)
    • Related Report
      2010 Annual Research Report
  • [Presentation] iPS細胞迅速スクリーニング系としてのラット胎仔メタネフロン器官培養の可能性2010

    • Author(s)
      増田茂夫
    • Organizer
      第9回日本再生医療学会総会
    • Place of Presentation
      広島(広島国際会議場)
    • Related Report
      2009 Annual Research Report
  • [Presentation] Cotransplantation with MSCs improves engraftment of HSCs after autologous intra-bone marrow transplantation in nonhuman primates(YIA受賞口演)2010

    • Author(s)
      増田茂夫
    • Organizer
      第9回日本再生医療学会総会
    • Place of Presentation
      広島(広島国際会議場)
    • Related Report
      2009 Annual Research Report
  • [Presentation] 胎児腎臓原基の器官培養を利用した異種幹細胞スクリーニング -手技の仔細と蛍光イメージングパターンによる分類-2010

    • Author(s)
      杉本直美、増田茂夫, et al.
    • Organizer
      第9回日本再生医療学会総会
    • Place of Presentation
      広島(広島国際会議場)
    • Related Report
      2009 Annual Research Report
  • [Presentation] Safe and efficient expansion of human hematopoietic stem cells with Sendai virus vector expressing HoxB4 in fetal sheep.2009

    • Author(s)
      Masuda S
    • Organizer
      The 6th Nikko International Symposium
    • Place of Presentation
      栃木(自治医大)
    • Year and Date
      2009-11-07
    • Related Report
      2009 Annual Research Report
  • [Presentation] ヒツジ移植系でのHoxB4-過性発現型センダイウイルスベクターによるヒト造血幹細胞増幅効果と安全性評価2009

    • Author(s)
      増田茂夫
    • Organizer
      第8回自治医大シンポジウム
    • Place of Presentation
      栃木(自治医大)
    • Year and Date
      2009-08-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] 間葉系幹細胞(MSC)共移植による造血幹細胞の生着促進効果 -霊長類モデルを用いて-,協和発酵キリン2009

    • Author(s)
      増田茂夫
    • Organizer
      第10回細胞移植・遺伝子治療セミナー
    • Place of Presentation
      栃木(宇都宮東武ホテルグランデ)
    • Year and Date
      2009-05-14
    • Related Report
      2010 Final Research Report
  • [Presentation] IMPROVED ENGRAFTMENT OF GENE-MODIFIED HSC AFTER CO-TRANSPLANTATION WITH MSC IN NON-HUMAN PRIMATES.2009

    • Author(s)
      Masuda S
    • Organizer
      第15回日本遺伝子治療学会学術集会
    • Place of Presentation
      大阪(阪大コンベンションセンター)
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] Co-transplantation of MSCs improves the engraftment of HSCs in nonhuman primates.2009

    • Author(s)
      Masuda S
    • Organizer
      7th International Society for Stem Cell Research : Annual Meeting
    • Place of Presentation
      スペイン(バルセロナ)
    • Related Report
      2010 Final Research Report
  • [Presentation] Co-transplantation of MSCs improves the engraftment of HSCs in nonhuman primates.2009

    • Author(s)
      Masuda S
    • Organizer
      第7回幹細胞シンポジウム
    • Place of Presentation
      東京(泉ガーデンギャラリー)
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] Co-transplantation of MSCs improves the engraftment of HSCs in nonhuman prunates.2009

    • Author(s)
      Masuda S
    • Organizer
      7^<th> International Society for Stem Cell Research : Annual Meeting
    • Place of Presentation
      スペイン(バルセロナ)
    • Related Report
      2009 Annual Research Report
  • [Presentation] ヒツジ胎子への子宮内移植によるヒツジ/サルキメラの形成とその免疫学的機構の解明2009

    • Author(s)
      阿部朋行、増田茂夫, et al.
    • Organizer
      第102回日本繁殖生物学会大会
    • Place of Presentation
      奈良(近畿大学農学部)
    • Related Report
      2009 Annual Research Report
  • [Presentation] ヒツジ移植系でのHoxB4-過性発現型センダイウイルスベクターによるヒトHSC増幅効果と安全性評価2009

    • Author(s)
      増田茂夫
    • Organizer
      第71回日本血液学会総会
    • Place of Presentation
      京都(国立京都国際会館)
    • Related Report
      2009 Annual Research Report
  • [Presentation] Safe and efficient expansion of human HSC with Sendai virus vector expressing HoxB4 in fetal sheep.2009

    • Author(s)
      Masuda S
    • Organizer
      第51回米国血液学会総会
    • Place of Presentation
      アメリカ合衆国(ニューオリンズ)
    • Related Report
      2009 Annual Research Report
  • [Presentation] 霊長類モデルにおける間葉系幹細胞の共移植による造血幹細胞の生着促進効果2008

    • Author(s)
      増田茂夫
    • Organizer
      第7回自治医科大学シンポジウム
    • Place of Presentation
      栃木(自治医大)
    • Year and Date
      2008-08-30
    • Related Report
      2010 Final Research Report
  • [Presentation] 霊長類モデルにおける間葉系幹細胞の共移植による造血幹細胞の生着促進効果2008

    • Author(s)
      増田茂夫
    • Organizer
      第70回日本血液学会総会
    • Place of Presentation
      京都(国立京都国際会館)
    • Related Report
      2010 Final Research Report
  • [Presentation] Co-transplantation of MSC improves the engraftment of HSC after auto-iBMT in non-human primates.2008

    • Author(s)
      Masuda S
    • Organizer
      第50回米国血液学会総会(ASH)
    • Place of Presentation
      アメリカ合衆国(サンフランシスコ)
    • Related Report
      2010 Final Research Report
  • [Remarks] ホームページ等

    • URL

      http://netplus.nikkei.co.jp/ssbiz/_techno/_te090414.html

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://netplus.nikkei.co.jp/ssbiz/techno/te090414.html

    • Related Report
      2009 Annual Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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