Development of the system to expand hematopoietic stem cells using gene modification technique

• Project/Area Number: 15591014
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Sapporo Medical University
• Principal Investigator: MATSUNAGA Takuya Sapporo Medical University, School of Medicine, Assistant professor, 医学部, 講師 (70260768)
• Project Period (FY): 2003 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2003: ¥2,600,000 (Direct Cost: ¥2,600,000)
• Keywords: Immortalized stromal cells / Artificial bone marrow / Cord blood / CD 34+ cells / Red blood cells / Platelets / 不死化ヒトストローマ細胞

Research Abstract

New sources of red blood cells (RBC) and platelets (PLT) would improve the transfusion capacity of blood centers. We developed culture systems for producing large quantity of enucleated RBC (e-RBC) or PLT from CB in vitro: one unit e-RBC (2 x 10^<12> RBC) or 1.8 units PLT (3.6 x 10^<10> PLT) was obtained from one standard CB unit (corresponding to 2 x 10^6 CD34^+ cells) using coculture systems with hTERT-transfected human stromal cells. The hemoglobin (Hb) content of the e-RBC quantified by photometric determination was almost equivalent to that of adult blood RBC. Oxygen dissociation curves of e-RBC measured by Hemox-Analyzer was comparable to that of fresh adult blood RBC. Aggregation capabilities of PLT was comparable to that of fresh adult blood PLT. In conclusion, the e-RBC or PLT produced by large-scale culturing system from CB CD34^+ cells may be useful for acute blood loss.

Research Products

• [Journal Article] Decrease of Smad4 gene expression in patients with essential thrombocythaemia may cause an escape from suppression of megakaryopoiesis by transforming growth factor-b1 (TGF-b1). (2004)
  • Author(s): Kuroda H, Matsunaga T et al.
  • Journal Title: Br J Haematol 124 Pages: 211-220
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Indian hedgehog gene transfer augments hematopoietic support of human stromal cells including NOD/SCID-β2m-/- repopulating cells. (2004)
  • Author(s): Kobune M, Matsunaga T et al.
  • Journal Title: Blood 104 Pages: 1002-1009
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Fas-mediated apoptosome formation is dependent on reactive oxygen species derived from mitochondrial permeability transition in jurkat cells. (2004)
  • Author(s): Sato T, Matsunaga T et al.
  • Journal Title: J Immunol 173 Pages: 285-296
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Recovery of neutrophil count by ganciclovir in patients with chronic idiopathic neutropenia associated with cytomegalovirus infection in bone marrow stromal cells (2004)
  • Author(s): Hirayama Y, Matsunaga T et al.
  • Journal Title: Int J Hematol 79 Pages: 337-339
  • NAID: 10013082044
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Glutathione-S-transferase P1-1 protects aberrant crypt foci from apoptosis induced by deoxycholic acid. (2004)
  • Author(s): Nobuoka A, Matsunaga T et al.
  • Journal Title: Gastroenterology 127 Pages: 428-443
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Chemoprevention of colorectal cancer. (2004)
  • Author(s): Niitsu Y, Matsunaga T et al.
  • Journal Title: Cancer Chemother Pharmacol 54 Suppl 1
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Plasma GSTP1-1 as a prognostic factor in patients with advanced non-Hodgkin's lymphoma (stages III and IV). (2004)
  • Author(s): Katahira T, Matsunaga T et al.
  • Journal Title: Clin Cancer Res 10 Pages: 7934-7940
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Decrease of Smad4 gene expression in patients with essential thrombocythaemia may cause an escape from suppression of megakaryopoiesis by transforming growth factor-(31 (TGF-β1) (2004)
  • Author(s): Kuroda H, Matsunaga T, Terui T, Tanaka I, Takimoto R, Fujikawa K, Takayama T, Kato J, Hirayama Y, Sakamaki S, Kohda K, Niitsu Y.
  • Journal Title: Br J Haematol 124 Pages: 211-220
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Indian hedgehog gene transfer augments hematopoietic support of human stromal cells including NOD/SCID-β32m-/- repopulating cells (2004)
  • Author(s): Kobune M, Ito Y, Kawano Y, Sasaki K, Uchida H, Nakamura K, Dehari H, Chiba H, Takimoto R, Matsunaga T, Terui T, Kato J, Niitsu Y, Hamada H.
  • Journal Title: Blood 104 Pages: 1002-1009
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Fas-mediated apoptosome formation is dependent on reactive oxygen species derived from mitochondrial permeability transition in jurkat cells (2004)
  • Author(s): Sato T, Machida, T, Takahashi S, Iyama S, Sato Y, Kuribayashi K, Takada K, Oku T, Kawano Y, Okamoto T, Takimoto R, Matsunaga T, Takayama T, Takahashi M, Kato J, Niitsu Y.
  • Journal Title: J Immunol 173 Pages: 285-296
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Recovery of neutrophil count by ganciclovir in patients with chronic idiopathic, neutropenia associated with cytomegalovirus infection in bone marrow stromal cells (2004)
  • Author(s): Hirayama Y, Sakamaki S, Tsuji Y, Chiba H, Matsunaga T, Takimoto R, Kato J, Niitsu Y.
  • Journal Title: Int J Hematol 79 Pages: 337-339
  • NAID: 10013082044
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Glutathione-S-transferase P1-1 protects aberrant crypt foci from apoptosis induced by deoxycholic acid (2004)
  • Author(s): Nobuoka A, Takayama T, Miyanishi K, Sato T, Takanashi K, Hayashi T, Kukitsu T, Sato Y, Takahashi M, Okamoto T, Matsunaga T, Kato J, Oda M, Azuma T, Niitsu Y.
  • Journal Title: Gastroenterology 127 Pages: 428-443
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Chemoprevention of colorectal cancer (2004)
  • Author(s): Niitsu Y, Takayama T, Miyanishi K, Nobuoka A, Hayashi T, Kukitsu T, Takanashi K, Ishiwatari H, Abe T, Kogawa T, Takahashi M, Matsunaga T, Kato J.
  • Journal Title: Cancer Chemother Pharmacol 54 Suppl 1
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Plasma GSTP1-1 as a prognostic factor in patients with advanced non-Hodgkin's lymphoma (stages III and IV) (2004)
  • Author(s): Katahira T, Takayama T, Miyanishi K, Hayashi T, Ikeda T, Takahashi Y, Takimoto R, Matsunaga T, Kato J, Niitsu Y.
  • Journal Title: Clin Cancer Res 10 Pages: 7934-7940
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Ex vivo expansion of human umbilical cord blood hematopoietic progenitor cells using a co-culture system with human telomerase catalytic subunit (hTERT) transfected human stromal cell. (2003)
  • Author(s): Kawano Y, Matsunaga T et al.
  • Journal Title: Blood 101 Pages: 532-540
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Telomerized human multipotent mesenchymal cells can differentiate into hematopoietic and cobblestone area-supporting cells. (2003)
  • Author(s): Kobune M, Matsunaga T et al.
  • Journal Title: Exp Hematol 31 Pages: 1-8
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Thrombopoietin concentrations in peripheral blood correlated with platelet numbers in two patients with thrombocytopenia by chronic graft-versus-host disease. (2003)
  • Author(s): Hirayama Y, Matsunaga T et al.
  • Journal Title: Am J Hematol 73 Pages: 285-289
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Inhibition of type I procollagen production by tRNAVa1CTE-HSP47 ribozyme. (2003)
  • Author(s): Hagiwara S, Matsunaga T et al.
  • Journal Title: J Gene Med 5 Pages: 784-794
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Interaction between the leukemic cell VLA4 with stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia. (2003)
  • Author(s): Matsunaga T, Takemoto N et al.
  • Journal Title: Nature Med 9 Pages: 1158-1165
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Induction of PIG3 and NOXA through Acetylation of p53 at 320 and 373 Lysine Residues as a Mechanism for Apoptotic Cell Death by Histone Deacetylase Inhibitors. (2003)
  • Author(s): Terui T, Matsunaga T et al.
  • Journal Title: Cancer Res 63 Pages: 8948-8954
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Ex vivo expansion of human umbilical cord blood hematopoietic progenitor cells using a co-culture system with human telomerase catalytic subunit (hTERT) transfected human stromal cell (2003)
  • Author(s): Kawano Y, Kobune M, Yamaguchi M, Nakamura K, Ito Y, Sasaki K, Matsunaga T, Kato J, Chiba H, Ikebuchi K, Niitsu Y, Hamada H.
  • Journal Title: Blood 101 Pages: 532-540
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Telomerized human multipotent mesenchymal cells can differentiate into hematopoietic and cobblestone area-supporting cells (2003)
  • Author(s): Kobune M, Kawano Y, Ito Y, Chiba H, Nakamura K, Tsuda H, Sasaki K, Dehari H, Uchida H, Honmou O, Takahashi S, Bizen A, Takimoto R, Matsunaga T, Kato J, Kato K, Houkin K, Niitsu Y, Hamada H.
  • Journal Title: Exp Hematol 31 Pages: 1-8
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Thrombopoietin concentrations in peripheral blood correlated with platelet numbers in two patients with thrombocytopenia by chronic graft-versus-host disease (2003)
  • Author(s): Hirayama Y, Sakamaki S, Tsuji Y, Sagawa T, Chiba H, Matsunaga T, Kuroda H, Kusakabe T, Akiyama T, Kato J, Niitsu Y.
  • Journal Title: Am J Hematol 73 Pages: 285-289
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibition of type I procollagen production by tRNAValCTE-HSP47 ribozyme (2003)
  • Author(s): Hagiwara S, Nakamura K, Hamada H, Sasaki K, Ito Y, Kuribayashi K, Sato T, Sato Y, Takahashi M, Kogawa K, Kato J, Terui T, Takayama T, Matsunaga T, Taira K, Niitsu Y.
  • Journal Title: J Gene Med 5 Pages: 784-794
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Interaction between the leukemic cell VLA4 with stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia (2003)
  • Author(s): Matsunaga T, Takemoto N, Sato T, Takimoto R, Tanaka I, Fujimi A, Akiyama T, Kuroda H, Kawano Y, Kobune M, Kato J, Hirayama Y, Sakamaki S, Kohda K, Miyake K, Niitsu Y.
  • Journal Title: Nature Med 9 Pages: 1158-1165
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Induction of PIG3 and NOXA through Acetylation of p53 at 320 and 373 Lysine Residues as a Mechanism for Apoptotic Cell Death by Histone Deacetylase Inhibitors (2003)
  • Author(s): Terui T, Murakami K, Takimoto R, Takahashi M, Takada K, Murakami T, Minami S, Matsunaga T, Takayama T, Kato J, Niitsu Y.
  • Journal Title: Cancer Res 63 Pages: 8948-8954
  • Description: 「研究成果報告書概要(欧文)」より