2002 Fiscal Year Final Research Report Summary
Development of hematopoietic stem cell transplantation using in vitro expanded bone marrow stromal cells
| Project/Area Number |
13671071
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
MATSUNAGA Takuya Sapporo Medical University, School of Medicine, Assistant professor, 医学部, 講師 (70260768)
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| Co-Investigator(Kenkyū-buntansha) |
NIITSU Yoshiro Sapporo Medical University, School of Medicine, Professor, 医学部, 教授 (10045502)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Bone marrow stromal cells / Immortalized gene / Hematopoietic stem cell transplantation / Telomerase |
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| Research Abstract |
Aim : We synthesized the immortalized bone marrow stromal cells by transducing immortalized gene. We then examined the marrow suppression inhibitory effect of hematopoietic stem cell transplantation using in vitro expanded stromal cells.
Methods and Results : Primary cultured marrow stromal cells were transfected with immortalized gene (activated ras, SV40T, hTERT) by retrovirus vector. After expanding of hTERT transfected stromal cells (hTERT stroma), hTERT gene was excluded by adenovirus vector containing Cre-recombinase gene. The expanded stromal cells without hTERT gene were transplanted with bone marrow mononuclear cells (BMMNC) to syngeneic mice treated with high dose cyclophosphamide. The recovery from myelosuppression by BMMNC plus expanded stromal cells transplantation was faster than that of BMMNC alone transplantation.
Conclusion : It was demonstrated that hematopoietic stem cell transplantation using in vitro expanded bone marrow stromal cells is a promising marrow suppression inhibitory method after high dose chemotherapy.
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[Publications] Kohda K, Sakamaki S, Matsunaga T, Kuga T, Fujimi A, Konuma Y, Kusakabe T, Kogawa K, Akiyama T, Koike K, Hirayama Y, Sasagawa Y, Nojiri S, Hirata Y, Nishisato T, Niitsu Y: "Long-term survival and late-onset complications of cancer patients treated with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation"Int J Hematol. 73. 251-257 (2001)
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[Publications] Lu Y, Sakamaki S, Kuroda H, Kusakabe T, Konuma Y, Akiyama T, Fujimi A, Takemoto N, Nishiie K, Matsunaga T, Hirayama Y, Kato J, Kon S, Kogawa K, Niitsu Y: "Prevention of lethal acute graft-versus-host disease in mice by oral administration of T helper 1 inhibitor, TAK-603"Blood. 97. 1123-1130 (2001)
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[Publications] Fujimi A, Matsunaga T, Kogawa K, Ohnuma T, Takahira N, Abe T, Kitaoka K, Kogawa K, Tanaka I, Morii K, Terui K, Sakamaki S, Kato J, Kura T, Maeda T, Niitsu Y: "A patient with paroxysmal nocturnal haemoglobinuria in whom G-CSF administration was remarkably effective against cellular immunodeficiency resulting in improvement of recurrent enterocolitis and its associated haemolytic attacks"Br J Haematol. 119. 858-862 (2002)
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[Publications] Hirayama Y, Sakamaki S, Matsunaga T, Kuroda H, Kusakabe T, Akiyama T, Kato J, Kogawa K, Koyama R, Nagai T, Ohta H, Niitsu Y: "Granulocyte-colony stimulating factor enhances the Expression of Transforming growth factor-beta mRNA in CD4-positive peripheral blood lymphocytes in the donors for allogeneic peripheral blood stem cell transplantation"Am J Hematol. 69. 138-140 (2002)
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[Publications] Sasaki H, Sato T, Yamauchi N, Okamoto T, Kobayashi D, Iyama S, Kato J, Matsunaga T, Takimoto R, Takayama T, Kogawa K, Watanabe N, Niitsu Y: "Induction of heat shock protein 47 synthesis by TGF-beta and IL-1beta via enhancement of the heat shock element binding activity of heat shock transcription factor 1"J Immunol. 168. 5178-5183 (2002)
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[Publications] Kawano Y, Kobune M, Yamaguchi M, Nakamura K, Ito Y, Sasaki K, Takahashi S, Nakamura T, Chiba H, Sato T, Matsunaga T, Azuma H, Ikebuchi K, Ikeda H, Kato J, Niitsu Y, Hamada H: "Ex vivo expansion of human umbilical cord hematopoietic progenitor cells using a coculture system with human telomerase catalytic subunit (hTERT)-transfected human stromal cells"Blood. 101. 532-540 (2003)
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[Publications] 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: "Inhibition of type I procollagen production by tRNAVa1CTE-HSP47 ribozyme"J Gene Med. (in press). (2003)
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