Control of the HSC Niche Signaling for the Efficient Long-Term Engraftment of Hematopoietic Stem Cells without Irradiation or High-Dose Chemotherapy

2010 Fiscal Year Final Research Report

• Project/Area Number: 21791003
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: Keio University
• Principal Investigator: YOSHIHARA Hiroki Keio University, 政策・メディア研究科, 助教 (90348706)
• Project Period (FY): 2009 – 2010
• Keywords: 移植・再生医療 / プロテオーム

Research Abstract

Irradiation and high-dose chemotherapy followed by bone marrow transplantation (BMT) have been a routine treatment for hematological malignancies and solid tumors. These conditioning, however, should be minimized since the toxicity extends to all organs generating serious side effects. In the adult BM, HSCs interact with its microenvironment which supports the activity of HSCs to maintain quiescence or self-renew to provide blood cells throughout the lifetime of an individual. This particular microenvironment, called stem cell niche, is critical for the maintenance of HSCs. In this study, we manipulated the niche for efficient engraftment avoiding redundant side effects of conditionings. We found that AMM2 or interferon-alpha is a promising niche regulator for transplantation without irradiation or high dose chemotherapy. Achievement of non-irradiated BMT method will provide advancement in stem cell therapy overcoming serious side effects.

Research Products

• [Journal Article] リン酸化タンパク質の網羅的解析 (2010)
  • Author(s): 吉原宏樹、石濱泰
  • Journal Title: 病理と臨床 28(5) Pages: 512-517
• [Journal Article] Isolation and characterization of endosteal niche cell populations that regulate hematopoietic stem cells. (2010)
  • Author(s): Nakamura Y, Arai F, Iwasaki H, Hosokawa K, Kobayashi I, Gomei Y, Matsumoto Y, Yoshihara H, Suda T.
  • Journal Title: Blood. 116(9) Pages: 1422-1432
• [Journal Article] Knockdown of N-cadherin suppresses the long-term engraftment of hematopoietic stem cells. (2010)
  • Author(s): Hosokawa K, Arai F, Yoshihara H, Iwasaki H, Nakamura Y, Gomei Y, Suda T.
  • Journal Title: Blood. 116(4) Pages: 554-563
  • Peer Reviewed
• [Journal Article] Cadherin-based adhesion is a potential target for niche manipulation to protect hematopoietic stem cells in adult bone marrow. (2010)
  • Author(s): Hosokawa K, Arai F, Yoshihara H, Iwasaki H, Hembree M, Yin T, Nakamura Y, Gomei Y, Takubo K, Shiama H, Matsuoka S, Li L, Suda T.
  • Journal Title: Cell Stem Cell 6(3) Pages: 194-198
  • Peer Reviewed
• [Journal Article] Functional differences between two Tie2 ligands, angiopoietin-1 and -2, in regulation of adult bone marrow hematopoietic stem cells. (2010)
  • Author(s): Gomei Y, Nakamura Y, Yoshihara H, Hosokawa K, Iwasaki H, Suda T, Arai F.
  • Journal Title: Exp Hematol 38(2) Pages: 82-89
  • Peer Reviewed
• [Journal Article] Niche regulation of hematopoietic stem cells in the endosteum. (2009)
  • Author(s): Arai F, Yoshihara H, Hosokawa K, Nakamura Y, Gomei Y, Iwasaki H, Suda T.
  • Journal Title: Ann N Y Acad Sci 1176 Pages: 36-46
  • Peer Reviewed
• [Journal Article] IRF-2 protects quiescent HSCs from type-I interferon-dependent exhaustion. (2009)
  • Author(s): Sato T, Onai N, Yoshihara H, Arai F, Suda T, Ohteki T.
  • Journal Title: Nature Medicine 15(6) Pages: 696-700
  • Peer Reviewed
• [Presentation] Phosphoproteomic Profiling of Leukemia Cells. Session Type : Poster Session. (2010)
  • Author(s): Yoshihara H, Shimada H, Shima H, Tomita M, Ishihama Y.
  • Organizer: 15th Congress of the European Hematology Association
  • Place of Presentation: Barcelona, Spain.
  • Year and Date: 20100610-20100613
• [Book] Annual Review血液2010「生体内における造血幹細胞の動態」 (2010)
  • Author(s): 吉原宏樹、須田年生
  • Total Pages: 1-6
  • Publisher: 中外医学社