Research on aging of human hematopoietic stem cells

• Project/Area Number: 21591367
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kagoshima University
• Principal Investigator: KAWANO Yoshifumi 鹿児島大学, 医歯学総合研究科, 教授 (20260680)
• Co-Investigator(Kenkyū-buntansha): OKAMOTO Yasuhiro 鹿児島大学, 医学部歯学部附属病院, 講師 (30398002) ; SHINKODA Yuichi 鹿児島大学, 医学部・歯学部附属病院, 特任助教 (50457652)
• Co-Investigator(Renkei-kenkyūsha): HIRAO Atsushi 金沢大学, がん研究所, 教授 (90343350)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 造血幹細胞 / 造血幹細胞移植 / CD34陽性細胞 / 加齢 / 老化 / 転写因子 / ヒト造血幹細胞 / 造血細胞移植術 / 加齢現象 / IKAROS / CEPBPAα / リンパ球/骨髄球比 / 造血細胞移植 / リンパ球比率

Research Abstract

To investigate aging of human hematopoietic stem cells, we evaluated the expression levels The median age of the donors was 21 y(range 0.2-44y). The purity of CD34-positive cells was greater than 90%. Both target genes were quantitatively detected in all samples. There was an inverse correlation between the expression level of ikzf1 and the donor's age(r=-0.358, p=0.032). In contrast, there was no correlation between the expression level of cebpa and the donor's age. From the data, the mRNA level of ikzf1 in purified CD34-positive cells may reflect the age of HSCs in human bone marrow.

Research Products

• [Journal Article] Benzene Metabolite 1, 2, 4-Benzenetriol Induces Halogenated DNA and Tyrosines Representing Halogenative Stress in the HL-60 Human Myeloid Cell Line (2012)
  • Author(s): Takuro Nishikawa, Emiko Miyahara, Masahisa Horiuchi, Kimiko Izumo, Yasuhiro Okamoto, Yoshichika Kawai, Yoshifumi Kawano and Toru Takeuchi
  • Journal Title: Environ Health Perspect Volume: 120 Pages: 62-67
  • Peer Reviewed
• [Journal Article] Benzene Metabolite 1,2,4-Benzenetriol Induces Halogenated DNA and Tyrosines Representing Halogenative Stress in the HL-60 Human Myeloid Cell Line (2012)
  • Author(s): Nishikawa T, et al
  • Journal Title: Environmental Health Perspectives Volume: 120 Pages: 62-67
  • Peer Reviewed
• [Journal Article] Vascular endothelial growth factor corrected for platelet count and hematocrit is associated with the clinical course of aplastic anemia in children (2012)
  • Author(s): Kodama Y, et al
  • Journal Title: Int J Hematol Volume: (In press) Issue: 5 Pages: 494-499
  • DOI: 10.1007/s12185-012-1074-1
  • Peer Reviewed
• [Journal Article] Benzene Induces Cytotoxicity without Metabolic Activation (2011)
  • Author(s): Takuro Nishikawa Kimiko izumo, Emiko miyahara, Masahisa horiuchi, Yasuhiro okamoto, Yoshifumi Kawano, Toru Takeuchi
  • Journal Title: J Occup Health Volume: 53 Pages: 84-92
  • NAID: 10027959345
  • Peer Reviewed
• [Journal Article] Randomized Trial to Compare LSA2L2-Type Maintenance Therapy to Daily 6-Mercaptopurine and Weekly Methotrexate With Vincristine and Dexamethasone Pulse for Children With Acute Lymphoblastic Leukemia (2010)
  • Author(s): Yoshihisa Nagatoshi, Akinobu Matsuzaki, Aiko Suminoe, Hiroko Inada, Kouichiro Ueda, Kiyoshi Kawakami, Fumio Yanai, Hideki Nakayama, Hiroshi Moritake, Nobuyoshi Itonaga, Noriko Hotta, Kyoko Fujita, Yasufumi Hidaka, Takeharu Yamanaka, Yoshifumi Kawano, Jun
  • Journal Title: Pediatr Blood Cancer Volume: 55 Issue: 2 Pages: 239-247
  • DOI: 10.1002/pbc.22528
  • Peer Reviewed
• [Journal Article] Successful bone marrow transplantation for children with aplastic anemia based on a best-available evidence strategy (2010)
  • Author(s): Okamoto Y, Kodama Y, Nishikawa T, Yamaki Y, Mougi H, Masamoto I, Tanabe T, Shinkoda Y, Kawano Y.
  • Journal Title: Pediatr Transplant Volume: 14 Pages: 980-5
  • Peer Reviewed
• [Journal Article] Unexpectedly high AUC levels in a child who received intravenous busulfan before stem cell transplantation (2010)
  • Author(s): Nishikawa T, Okamoto Y, Tanabe T, Shinkoda Y, Kodama Y, Higashi M, Hirano H, Arita K, and Kawano Y.
  • Journal Title: Bone Marrow Transplant Volume: 45(3) Pages: 602-604
  • Peer Reviewed
• [Journal Article] Successful bone marrow transplantation for children with aplastic anemia based on a best-available evidence strategy. (2010)
  • Author(s): Okamoto Y, et al
  • Journal Title: Pediatric Transplantation. Volume: 14 Pages: 980-985
  • Peer Reviewed
• [Journal Article] Serum derivative of reactive oxygen metabolites (d-ROMs) in pediatric hemato-oncological patients with neutropenic fever. (2010)
  • Author(s): Nishikawa T, et al
  • Journal Title: Pediatric Blood and Cancer Volume: 55 Pages: 91-94
  • Peer Reviewed
• [Journal Article] Unexpectedly high AUC levels in a child who received intravenous busulfan before stem cell transplantation. (2010)
  • Author(s): Nishikawa T, et al
  • Journal Title: Bone Marrow Transplantion Volume: 45 Pages: 602-604
  • Peer Reviewed
• [Journal Article] Double apheresis of peripheral blood stem cells in a single day in children mobilized by granulocyte colony-stimulating factor for transplantation (2009)
  • Author(s): Okamoto Y, Watanabe T, Watanabe H, Onishi T, Kawano Y.
  • Journal Title: Pediatr Transplant Volume: 13(4) Pages: 440-443
  • Peer Reviewed
• [Presentation] Lymphoid commitment in human bone marrow CD34-positive cells reflects aging of hematopoietic stem cells (2011)
  • Author(s): Kodama Y, Miyazono A, Okamoto Y, Yamaki Y, Kurauchi K, Nishikawa T, Tanabe T, Shinkoda Y, Kawano Y.
  • Organizer: The 2nd Meeting of Asian Cellular Therapy Organization
  • Place of Presentation: Miyazaki
• [Presentation] HIF-1α is not associated with the clinical course of aplastic anemia in children (2011)
  • Author(s): Kodama Y, Okamoto Y, Shinkoda Y, Tanabe T, Nishikawa T, Yamaki Y, Kawano Y.
  • Organizer: The 73rd Annual Meeting of the Japanese Society of Hematology(JSH2011)
  • Place of Presentation: Nagoya
• [Presentation] Myeloperoxidase-derived halogenative stress, a possible cause of benzene leukemogenesis (2011)
  • Author(s): Nishikawa T, Izumo K, Miyahara E, Horiuchi M, Okamoto Y, Kawai Y, Kawano Y, Takeuchi T.
  • Organizer: The 73rd Annual Meeting of the Japanese Society of Hematology(JSH2011)
  • Place of Presentation: Nagoya
• [Presentation] Continued Complete Remissions in 3 ALL patients who received under optimal chemotherapy (2011)
  • Author(s): Okamoto Y, Yamaki Y, Nishikawa T, Kodama Y, Shinkida Y, Tanabe T, Kawano Y.
  • Organizer: The 73rd Annual Meeting of the Japanese Society of Hematology(JSH2011)
  • Place of Presentation: Nagoya
• [Presentation] Lymphoid commitment in human bone marrow CD34-positive cells reflects aging of hematopoietic stem cells (2011)
  • Author(s): Kodama Y, et al
  • Organizer: The 2^<nd> Meeting of Asian Cellular Therapy Organization
  • Place of Presentation: Miyazaki