Clarification of the mechanism of differentiation from hematopoietic stem cell-derived cells to hepatic stellate cells

2010 Fiscal Year Final Research Report

• Project/Area Number: 20591150
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Mie University
• Principal Investigator: MASUYA Masahiro Mie University, 大学院・医学系研究科, 准教授 (30281083)
• Project Period (FY): 2008 – 2010
• Keywords: 単球 / 分化 / 肝星細胞 / MCP-1 / CCR2

Research Abstract

We previously clarified that hematopoietic stem cell-derived cells were abele to differentiate into hepatic stellate cells (HpSCs) during carbon tetrachloride (CCl_4)-induced iver injury. Which lineage of cells are true precursors of HpSCs remains unknown. We idoptively transferred neutrophils, monocytes, eosinophils, B cells, or T cells, which were isolated rom enhanced green fluorescent protein (EGFP)-transgenic mice, into CCl_4-injured non-transgenic nice. In the livers of mice given monocytes, EGFP^+ HpSCs were detected. This suggest that a proportion of monocytes are precursors of HpSCs. Monocyte chemoattractant protein-1 (MCP-1) is bought to be associated with the invasion of monocytes into injured liver. CCR2, a receptor for vICP-1, is expressed on monocytes. We examined the effect of CCR2 antagonist against the lifferentiation of monocytes into HpSCs and found that the antagonist suppressed the number of EGFP^+ HpSCs and the area of fibrosis in injured liver.

Research Products

• [Journal Article] Thrombocytopenia in mice lacking the carboxy-termainal regulatory domain of the Ets transcription factor Flil (2010)
  • Author(s): Moussa O, LaRue AC, Abangan RS Jr, Williams CR, Zhang XK, Masuya M, Gong YZ, Spyropoulos DD, Ogawa M, Gilkeson G, Watson DK
  • Journal Title: Mol Cell Biol Vol.30, No.21 Pages: 5194-5206
  • Peer Reviewed
• [Journal Article] An efficient method for single hematopoietic stein cell engraftment in mice based on cell-cycle dormancy of hematopoietic stem cells (2010)
  • Author(s): Abe T, Masuya M, Ogawa M
  • Journal Title: Exp Hematil Vol.38, No.7 Pages: 603-608
  • Peer Reviewed
• [Journal Article] Drug interaction between itraconazole and bortezomib : exacerbation of peripheral neuropathy and thrombocytopenia induced by bortezomib (2010)
  • Author(s): Iwamoto T, Ishibashi M, Fujieda A, Masuya M, Katayama N, Okuda M
  • Journal Title: Pharmacotherapy Vol.30, No.7 Pages: 661-665
  • Peer Reviewed
• [Journal Article] Diagnostic value of PCR analysis of bacteria and fungi from blood in empiric-therapy-resistant febrile neutropenia (2010)
  • Author(s): Nakamura A, Sugimoto Y, Ohishi K, Sugawara Y, Fujieda A, Monma F, Suzuki K, Masuya M, Nakase K, Matsushima Y, Wada H, Katayama N, Nobori T
  • Journal Title: J Clin Microbiol Vol.48, No.6 Pages: 2030-2036
  • Peer Reviewed
• [Journal Article] A potential activity of valproic acid in the stimulation of interleukin-3-mediated megakaryopoiesis and erythropoiesis (2010)
  • Author(s): Liu B, Ohishi K, Yamamura K, Suzuki K, Monma F, Ino K, Nishii K, Masuya M, Sekine T, Heike Y, Takaue Y, Katayama N
  • Journal Title: Exp Hematol Vol.38, No.8 Pages: 685-695
  • Peer Reviewed
• [Journal Article] Effect of washing solution on platelet counts following transfusion with twice-washed platelets : a single-patient experience (2010)
  • Author(s): Tanaka Y, Ohishi K, Yonekawa T, Yodoya N, Iwamoto S, Nishioka Y, Tatara Y, Matsumoto T, Masuya M
  • Journal Title: Transfusion Med Vol.20, No.5 Pages: 358-360
  • Peer Reviewed
• [Journal Article] High-intensity signals in the basal ganglia from gadolinium-enhanced T1-weighted MRI as an early change in toxoplasma encephalitis in an AIDS patient (2010)
  • Author(s): Suzuki K, Masuya M, Matsumoto T, Ito N, Ohishi K, Maeda M, Katayama N
  • Journal Title: J Infect Chemother Vol.16, No.2 Pages: 135-138
  • Peer Reviewed
• [Journal Article] 同種末梢血幹細胞移植後長期間無再発生存中のアグレッシブNK細胞白血病 (2010)
  • Author(s): 伊野和子、桝屋正浩、中森良樹、鈴木圭、水谷実、関根隆夫、山口素子、中瀬一則、海田勝二、小川啓恭、片山直之
  • Journal Title: 臨床血液 51巻、4号 Pages: 258-263
  • Peer Reviewed
• [Journal Article] The effectiveness of measuring for fragmented red cells using an automated hematology analyzer in patients with thrombotic microangiopathy (2009)
  • Author(s): Abe Y, Wada H, Yamada E, Noda M, Ikejiri M, NIshioka J, Kobayashi T, Matsumoto T, Masuya M, Isaji S, Usui M, Uemoto S, Katayama N, Nobori T
  • Journal Title: Clin Appl Thromb Hemost Vol.15, No.2 Pages: 257-262
  • Peer Reviewed
• [Journal Article] Dual topology of functional Toll-like receptor 3 expression in human hepatocellular carcinoma (2008)
  • Author(s): Yoneda K, Sugimoto K, Shiraki K, Tanaka J, Beppu T, Fuke H, Yamamoto N, Masuya M, Horie R, Uchida K, Takei Y
  • Journal Title: differential signaling mechanisms of TLR3-induced NF-kappaB activation and apoptosis Vol.33, No.5 Pages: 929-936
  • Peer Reviewed
• [Journal Article] Deletion of chromosome arm 15q in a case of minimally differentiated hypoplastic AML-M0 (2008)
  • Author(s): Fujieda A, Masuya M, Kitano S, Miyazaki K, Yazaki A, Sugimoto Y, Usui E, Miyata E, Shibasaki T, Yamamura K, Ohishi K, Nishii K, Nakase K, Takeuchi Tm, Katayama N
  • Journal Title: Cancer Genet Cytogenet Vol.184, No.1 Pages: 57-61
  • Peer Reviewed
• [Journal Article] ADAMTSI3 related markers and von Willebrand factor in plasma from patients with thrombotic microangiopathy (TMA) (2008)
  • Author(s): Kobayashi T, Wada H, Nishioka J, Yamamoto M, Matsumoto T, Tamara T, Nomura S, Masuya M, Mori Y, Nakatani K, Nishikawa M, Katayama N, Nobori T
  • Journal Title: Thromb Res Vol.121, No.6 Pages: 849-854
  • Peer Reviewed
• [Presentation] Important role for flt3 Ligand in the generation of early B and T cell precursors from human primitive hematopoietic progenitors, revealed by telomerized human stromal cells (2010)
  • Author(s): Liu B, Ohishi K, Masuya M, Hamada H, Katayama N
  • Organizer: 52nd American Society of Hematology Meeting
  • Place of Presentation: Orland, FL, USA (Poster)
  • Year and Date: 2010-12-05
• [Presentation] Hematopoietic origin of pancreatic stellate cells (2010)
  • Author(s): 伊野和子、桝屋正浩、宮田恵里、大有晃嗣、片山直之
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜、口演
  • Year and Date: 2010-09-24
• [Presentation] Ly6C^+ inflammatory monocytes are extrahepatic precursors of hepatic stellate cells in liver injury (2009)
  • Author(s): Masuya M, Araki H, Ohishi K, Katayama N
  • Organizer: 51th Annual Meeting of American Society of Hematology
  • Place of Presentation: New Orleans, USA (Poster)
  • Year and Date: 20091204-20091208
• [Presentation] Evaluation of potential role for valproic acid in IL-3-mediated megakaryopoiesis and erythropoiesis in serum-free and serum-containing cultures (2009)
  • Author(s): Ohishi K, Liu B, Masuya M,, Heike Y, Takaue Y, Katayama N
  • Organizer: 51th Annual Meeting of American Society of Hematology
  • Place of Presentation: New Orleans, LA, USA (Poster)
  • Year and Date: 20091204-20091208
• [Presentation] Transfusion of platelet concentrates washed twice with M-sol provided adequatepost-transfusion platelet count increments in an anhaptoglobinemic patient with anti-haptoglobin antibody (2009)
  • Author(s): Tanaka Y, Kassai C, Abe K, Nishio M, Maruyama M, Kamada N, Matsumoto T, Masuya M, Nishioka Y, Tatara Y, Ohishi K
  • Organizer: The XXth Regional Congress of the International Society Blood Transfusion (ISBT) Asia
  • Place of Presentation: Nagoya, Japan (Poster)
  • Year and Date: 20091114-20091118
• [Presentation] Valproic acid, in combination with IL-3, stimulates human megakaryopoiesis as well as erythropoiesis (2009)
  • Author(s): Ryuu H, Ohishi K, Masuya M, Heike Y, Takaue Y, Katayama N
  • Organizer: 第71回日本血液学会
  • Place of Presentation: 京都、口演
  • Year and Date: 20091021-20091023
• [Presentation] Ly6C+単球は肝傷害時の肝星細胞の前駆細胞である (2009)
  • Author(s): 桝屋正浩、大石晃嗣、片山直之
  • Organizer: 第68回日本癌学会総会
  • Place of Presentation: 横浜、ポスター
  • Year and Date: 20091001-20091003
• [Presentation] MLL-ENL融合遺伝子による形質転換は造血幹細胞のみを標的として生じる (2009)
  • Author(s): 小埜良一、桝屋正浩、宮田恵里、中島秀明、上迫努、伊藤守、鈴木圭、片山直之、北村俊雄、野坂哲哉
  • Organizer: 第68回日本癌学会総会
  • Place of Presentation: 横浜、口演
  • Year and Date: 20091001-20091003
• [Presentation] IFN-αはPI3Kを介して造血前駆細胞のβ1インテグリンによる細胞接着を増強する (2008)
  • Author(s): 桝屋正浩、大石晃嗣、中村志帆、宮田恵里、杉本由香、藤枝敦史、片山直之
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都、ポスター
  • Year and Date: 20081010-20081012
• [Presentation] 血液疾患患者における末梢血細菌・真菌PCR検査の有用性の検討 (2008)
  • Author(s): 杉本由香、中村明子、大石晃嗣、宮田恵里、門間文彦、田丸智巳、藤枝敦史、山口素子、西井一浩、桝屋正浩、中瀬一則、松島佳子、和田英夫、登勉、片山直之
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都、口演
  • Year and Date: 20081010-20081012
• [Presentation] ヒト巨核球系前駆細胞の分化・増殖におけるヒストン脱アセチル化酵素の役割 (2008)
  • Author(s): 大有晃嗣、山村賢太郎、桝屋正浩、平家勇司、高上洋一、片山直之
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都、口演
  • Year and Date: 20081010-20081012
• [Presentation] 輸血細菌感染症対策細菌迅速遺伝子診断システムを用いた初流血除去の細菌除去効果の判定 (2008)
  • Author(s): 阿部久美子、田中由美、今井重美、丸山美津子、葛西千枝子、西尾緑、信田憲行、森口洋子、和田英夫、大石晃嗣、小島精、登勉、桝屋正浩
  • Organizer: 第56回輸血・細胞治療学会総会
  • Place of Presentation: 福岡、口演
  • Year and Date: 20080425-20080427