1999 Fiscal Year Final Research Report Summary
Establishment of Novel Method for Hematopoietic Stem Cell Transplantation Using Thioredoxin-Gene Transfer Technique
| Project/Area Number |
10670967
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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 | Keio University |
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Principal Investigator |
HATTORI Yutaka Keio Univ., Hematology, Instructor, 医学部, 助手 (20189575)
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| Co-Investigator(Kenkyū-buntansha) |
IKEDA Yasuo Keio Univ., Hematology, Professor, 医学部, 教授 (00110883)
KIZAKI Masahiro Keio Univ., Hematology, Assistant Professor, 医学部, 講師 (20161432)
KAMATA Tamihiro Keio Univ., Hematology, Instructor, 医学部, 助手 (90265794)
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| Project Period (FY) |
1998 – 1999
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| Keywords | thioredoxin / hematopoietic stem cell transplantation / gene therapy / drug resistance |
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| Research Abstract |
Thioredoxin (TRX), a redox regulator, is known to reduce oxygen stress which is caused by the use of antineoplastic drug or irradiation. Based on this knowledge, we challenged to establish a novel method to protect bone marrow cells from cell damage caused by chemotherapy or irradiation therapy by TRX-gene transfer. In 1998, TRX-gene expression was examined in a number of hematopoietic cell lines. Every cell expressed very weakly the endogenous TRX-transcripts. TRX gene was then induced to NIH3T3 fibroblast and was examined acquisition of drug resistance. TRX transfectants were cloned and revealed slight resistance to HィイD22ィエD2OィイD22ィエD2, cisplatinum and 4-hydroxycyclofosfamide. TRX-gene was then induced to hematopoietic cells including bone marrow cells. However, it was so difficult to obtain TRX-induced hematopoietic cells probably because of low induction efficiency. In 1999, to overcome this technical difficulty we successfully established unique system by co-induction of keratinocyte growth factor (KGF) receptor-gene, K-sam. Namely, after K-sam-gene trdansfer to hematopoietic cell lines as well as murine bone marrow cells, the cells were stimulated with K-sam-ligand, KGF. By this method, k-sam-induced cells were preferentially amplified. Incidentally, it was also found that KGF stimulation did not occur induction of differentiation and did not alter characteristics of the cells. Therefore, this method is considered to be a novel efficient model for hematopoietic stem cell expansion, and the clinical application is expected.
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