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Long-term bone marrow culture-derived stromal fibroblasts as a potential target for gene therapy in acute myelogenous leukemia.

Authors
 Yoo Hong Min  ;  Guang Xun Li  ;  Joon Ho Jang  ;  Hyung Chan Suh  ;  Jin Seok Kim  ;  June Won Cheong  ;  Seung Tae Lee  ;  Jee Sook Hahn  ;  Yun Woong Ko 
Citation
 LEUKEMIA RESEARCH, Vol.26(4) : 369-376, 2002 
Journal Title
LEUKEMIA RESEARCH
ISSN
 0145-2126 
Issue Date
2002
MeSH
Adenoviridae ; Bone Marrow Cells/pathology* ; Bone Marrow Cells/physiology ; Bone Marrow Transplantation ; Genetic Engineering ; Genetic Therapy*/methods ; Genetic Vectors ; Humans ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/pathology* ; Leukemia, Myeloid, Acute/therapy ; Stromal Cells/pathology* ; Stromal Cells/physiology ; Time Factors ; Transduction, Genetic* ; Transplantation, Autologous ; Tumor Cells, Cultured*
Keywords
Bone marrow ; Stromal fibroblast ; Acute myelogenous leukemia ; Gene therapy
Abstract
As a part of our continuing efforts to develop gene therapy for acute myelogenous leukemia (AML), this study was undertaken to evaluate the possibility of using autologous bone marrow stromal fibroblasts (BMSFs) as a target cell population. Autologous BMSFs in AML were isolated from the stromal layers of long-term bone marrow culture (LTBMC) using immunomagnetic beads. BMSFs exhibited rapid proliferation even in the absence of growth factors. Cultures stimulated with bFGF produced significantly increased numbers of BMSFs than cultures without added growth factors. Using LNC/LacZ retroviral vector, the transduction efficiecy of BMSFs was 13±4% at a 5 multiplicity of infection (MOI). LNC/interleukin-2 (IL-2)-transduced BMSFs produced between 1200 and 4800 pg of IL-2/106 cells per 24 h. Using adenoviral vector AdV/LacZ, the transduction efficiency was 84±10% at 100, and 92±8% at a MOI of 1000. Although the addition of basic fibroblast growth factor, epidermal growth factor, or platelet-derived growth factor did not affect the transduction efficiency, they increased the numbers of transduced cells significantly (P<0.01). AdV/IL-2-treated BMSFs produced high levels of IL-2 over the course of 7 days between 9820 and 22,700 pg of IL-2/106 cells per 24 h. Our finding that the genetically engineered autologous BMSFs of AML could be successfully established in vitro implies that BMSFs obtained from LTBMC might be considered as a target cell population for certain types of clinical gene therapy in AML.
Full Text
http://www.sciencedirect.com/science/article/pii/S0145212601001345
DOI
10.1016/S0145-2126(01)00134-5
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Min, Yoo Hong(민유홍) ORCID logo https://orcid.org/0000-0001-8542-9583
Cheong, June-Won(정준원) ORCID logo https://orcid.org/0000-0002-1744-0921
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/144505
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