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The growth of K562 human leukemia cells was inhibited by therapeutic neural stem cells in cellular and xenograft mouse models
Authors:GEON-TAE PARK  JAE-RIM HEO  SEUNG U. KIM  KYUNG-CHUL CHOI
Affiliation:1. Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea;2. Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada;3. Institute of Life Science and Bio-Engineering, TheraCell Bio & Science, Cheongju, Chungbuk, Republic of Korea
Abstract:To confirm the anti-tumor effect of engineered neural stem cells (NSCs) expressing cytosine deaminase (CD) and interferon-β (IFN-β) with prodrug 5-fluorocytosine (FC), K562 chronic myeloid leukemia (CML) cells were co-cultured with the neural stem cell lines HB1.F3.CD and HB1.F3.CD.IFN-β in 5-FC containing media. A significant decrease in the viability of K562 cells was observed by the treatment of the NSC lines, HB1.F3.CD and HB1.F3.CD.IFN-β, compared with the control. A modified trans-well assay showed that engineered human NSCs significantly migrated toward K562 CML cells more than human normal lung cells. In addition, the important chemoattractant factors involved in the specific migration ability of stem cells were found to be expressed in K562 CML cells. In a xenograft mouse model, NSC treatments via subcutaneous and intravenous injections resulted in significant inhibitions of tumor mass growth and extended survival dates of the mice. Taken together, these results suggest that gene therapy using genetically engineered stem cells expressing CD and IFN-β may be effective for treating CML in these mouse models.
Keywords:chronic myeloid leukemia  cytosine deaminase  interferon-β  neural stem cell
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