Understanding of mechanism of human lymphopoiesis and clinical application to cell therapy

• Project/Area Number: 21591240
• 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: OHISHI Kohshi 三重大学, 医学部附属病院, 講師 (00397506)
• Co-Investigator(Kenkyū-buntansha): NISHIKAWA Hiroyoshi 大阪大学, 免疫フロンティア研究センター, 特任准教授 (10444431)
• Co-Investigator(Renkei-kenkyūsha): NOSAKA Tetsuya (30218309)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: Tリンパ球 / Bリンパ球 / 分化 / ストローマ細胞 / ヒト骨髄ストローマ細胞 / Bリンパ球分化 / Tリンパ球分化 / flt3 ligand / stem cell factor / thombopoietin / 細胞接着 / NKリンパ球分化 / stromal cells / ProB cells / T/NK cell precursors / hematopoiesis / cord blood / lymphopoiesis / differentiation / stromal cell / ProB cell / ProT cell / thrombopoietin

Research Abstract

Telomerized human bone marrow stromal cells supported the simultaneous generation of CD19^+ CD10^+ cyCD79a^+ CD20^+/-VpreB^-proB and CD7^+ CD45RA^+ CD56^-cyCD3-early T/NK cell precursors from human hematopoietic progenitors. The generation of both lymphoid precursors was promoted by flt3 ligand. Early B and T/NK development could occur without direct contact with stromal cells. We also examined the role of Delta ligand expression on the stromal cells in T cell differentiation and clinical application to T cell therapy.

Research Products

• [Journal Article] Human bone marrow stromal cells simultaneously support B and T/NK lineage development from human haematopoietic progenitors A principal role for flt3 ligand in lymphopoiesis (2012)
  • Author(s): Nakamori Y, Liu B, Ohishi K, Suzuki K, Ino K, Matsumoto T, Masuya M, Nishikawa H, Shiku H, Hamada H, Katayama N
  • Journal Title: Br J Haematol Volume: 157(6) Pages: 674-86
  • Peer Reviewed
• [Journal Article] Human bone marrow stromal cells simultaneously support B and T/NK lineage development from human haematopoietic progenitors : A principal role for flt3 ligand in lymphopoiesis (2012)
  • Author(s): Nakamori Y, Liu B, Ohishi K, Suzuki K, Ino K, Matsumoto T, Masuya M, Nishikawa H, Shiku H, Hamada H, Katayama N
  • Journal Title: British Journal of haematology Volume: (In Press)
  • 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 Volume: 38 Pages: 685-695
  • Peer Reviewed
• [Journal Article] A potential activity of valproic acid in the stimulation of interleukin-3-mediated meoakaryopoiesis and erythropoiesis. (2010)
  • Author(s): Liu B, Ohishi K, et al.
  • Journal Title: Exp Hematol Volume: 38 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, et al.
  • Journal Title: Transfus Med. Volume: 20 Pages: 358-360
  • 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, et al.
  • Journal Title: J Clin Microbiol. Volume: 48 Pages: 2030-2036
  • Peer Reviewed
• [Presentation] Evaluation of Role for flt3L in Human Early B and T/NK Lymphopoiesis in a Novel Stromal Cell Culture System (2011)
  • Author(s): Nakamori Y, Ohishi K, Liu B, Masuya M, Mamada H, Katayama N
  • Organizer: 53^<rd> ASH annual Meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 2011-12-12
• [Presentation] Evaluation of role for flt3 ligand in human lymphopoiesis with telomerized human stromal cells (2011)
  • Author(s): 中森良樹大石晃嗣劉氷桝屋正浩濱田洋文片山直之
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-15
• [Presentation] Evaluation of Role for flt3L in Human Early B and T/NK Lymphopoiesis in a Novel Stromal Cell Culture System (2011)
  • Author(s): Nakamori Y, Ohishi K, Liu B, Masuya M, Hamada H, Katayama N
  • Organizer: 53rd ASH annual Meeting and Exposition
  • Place of Presentation: San Diego, USA
• [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: 54nd American Society of Hematology Meeting
  • Place of Presentation: Orland, FL, USA
  • Year and Date: 2010-12-05
• [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: 54nd American Society of Hematology Meeting
  • Place of Presentation: Orland, FL, USA
  • Year and Date: 2010-12-05
• [Presentation] Crucial role of flt3 ligand in human early B/T lymphopoiesis revealed by telomerized stromal cells (2009)
  • Author(s): Liu B, Ohishi K, Suzuki K, Masuya M, Hamada H, Nishikawa H, Shiku H, and Katayama N
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-24
• [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: 51st ASH Annual Meeting
  • Place of Presentation: New Orleans, LA, USA
• [Presentation] Evaluation of potential role for Valproic Acid in IL-3-mediated megakary opoiesis and erythropoiesis in serum-free and serum-containing cultures (2009)
  • Author(s): Ohishi K, et al
  • Organizer: 51st ASH Annual Meeting
  • Place of Presentation: New Orleans, LA, USA
• [Presentation] Valproic acid, in combination with IL-3, stimulates human megakaryopoiesis as well as erythropoiesis (2009)
  • Author(s): Ryuu H, Ohishi K, et al
  • Organizer: 第71回日本血液学会
  • Place of Presentation: 京都
• [Presentation] HDAC inhibitors exert stimulatory effects on human megakaryopoiesis or erythropoiesis in the presence of IL-3 or GM-CSF (2009)
  • Author(s): Ohishi K
  • Organizer: 第68回日本癌学会
  • Place of Presentation: 横浜