Hematopoietic Differentiation of Induced Pluripotent Stem Cells (iPSCs) derived from Glioblastoma Cell Lines

Establishment of pluripotent stem cells provides a comprehensive model to study early hematopoietic development and has emerged as a powerful research tool to explore regenerative medicine. Owing to a shortage of donors and a limited number of the cells, hematopoietic cell induction from pluripotent stem cells has been regarded as an alternative source of hematopoietic stem cells (HSCs) and mature hematopoietic cells for intended therapeutic purposes. Generation of induced pluripotent stem cells (iPSCs) has been described as a powerful method to dedifferentiate the specialized cells to pluripotency. Particularly, the generation of induced pluripotent cancer cells (iPC) allows us to access a valuable experimental platform in order to mimic oncogenesis process and harbours a great potential regarding drug screening as well as differentiation studies and personalized medicine; however, obtaining iPCs is encountered to several barriers. To help overcome this difficulty in the iPC generation we have tried to set up an optimized method to generate iPC from in vitro transformed cell lines representing the aggressive form of brain tumor-glioblastoma- and to understand the potential barriers ahead of efficient generation of iPCs. Our findings confirmed a resistant identity of cancer cells to achieve the pluripotency markers. Furthermore, besides designing technical tricks to obviate the barriers ahead of iPC generation, we have suggested using the small molecule PD98059 to enhance the efficiency of iPC generation from glioblastoma cell lines. Our data also confirmed that while T653 cell line harbouring an overactive form of Ras oncogene reprogram into iPC cells the activity of oncoprotein Ras is significantly suppressed, a down-regulation which is sustained following the hematopoietic differentiation. Further studies are required to standardize the methods of iPC cell generation and differentiation for future regenerative medicine.

کلیدواژه ها:

Hematopoietic differentiation ، Induced pluripotent cancer cells ، Glioblastoma