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Generation of Induced Pluripotent Cancer Cells From Glioblastoma Multiform Cell Lines Publisher Pubmed



Vatanmakanian M1 ; Yousefi H2 ; Mashouri L3 ; Aref AR4 ; Khamisipour G5 ; Bitaraf A6 ; Alizadeh S1
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Authors Affiliations
  1. 1. Department Hematology, School of Allied Medical Sciences, Tehran University of Medical Sciences, Qods Street, Tehran, 1416753955, Iran
  2. 2. Department of Biochemistry and Molecular Biology, LSUHSC, School of Medicine, New Orleans, LA, United States
  3. 3. Department of Genetics, University of Shahrekord, Shahrekord, Iran
  4. 4. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States
  5. 5. Department of Hematology, School of Allied Medical Sciences, Bushehr University of Medical Sciences, Bushehr, Iran
  6. 6. Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

Source: Cellular Reprogramming Published:2019


Abstract

Generation of induced pluripotent stem cells (iPSCs) has been described as a powerful method to dedifferentiate the specialized cells to pluripotency. However, obtaining cancer-specific iPS cells (iPCs) encounters several barriers. The generation of iPCs provides valuable experimental platforms to mimic oncogenesis and offers potentials regarding drug screening. To overcome the difficulties regarding the iPC generation, we aimed at optimizing the generation of iPCs from glioblastoma multiform (GBM) cell lines and at understanding the potential barriers ahead of this process. The T731, T653, and mouse embryonic fibroblast cells were transduced by using retroviral plasmids encoding Oct4, Sox2, and Klf4. The cells were cultured on a layer of feeder cells for 14 days in iPS media and the obtained colonies were then picked and expanded to be evaluated for pluripotency markers by alkaline phosphatase staining, qRT-PCR, and Western blotting. Our findings confirmed resistance in cancer cells to achieve the pluripotency markers. In addition to designing technical tricks to obviate the barriers ahead of iPC generation, we suggested the small molecule PD98059 to enhance the efficiency of iPC generation from GBM cell lines. The resulting iPCs can further be used as a platform to study the mechanism of cancer formation and as a tool for drug screening for the treatment of patients with GBM. © Copyright 2019, Mary Ann Liebert, Inc., publishers 2019.
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