REPROGRAMMING IPSC INTO STEM CELLS, A POSSIBLE TURNING POINT FOR CANCER THERAPY
Led by Inan Olmez at Vanderbilt University Medical Center
There is growing amount of data that anaplastic gliomas and Glioblastoma Multiforme (GBM) originate from cancer stem cells. These cells cause tumor growth through proliferation and aberrant differentiation. Unlike differentiated tumor cells, cancer stem cells are resistant to traditional chemotherapy and radiation therapies. This may be why patients generally either fail to respond or present with recurrence of their
disease. Isolation of cancer stem cells will enable us to understand the pathways responsible for resistance to current therapies and to develop new treatment options. Unfortunately, methods for isolating cancer stem cells from resected tumor mass are not efficient.
Although the exact source of cancer stem cells is unknown, they are most likely derived either from normal stem cells or tissue-specific differentiated cells. Stem cells reside in a microenvironment and are supported by many other cells through cytokines and ligands. This is termed stem cell “niche”, and is an active area of investigation as alteration of the normal stem cell niche could result in cancer stem cell formation.
In our lab, we generate human induced pluripotent stem cells (iPSCs) by transient transfection of primary fibroblasts. These iPSCs do not have any residual DNA. Since fibroblasts can be induced to become stem cell, I hypothesize that iPSCs could be converted epigenetically into cancer stem cells by exposing them to cancer microenvironment. If this approach is successful, we can develop patient-specific cancer stem cells from resected tumor cells and screen such cancer stem cellsfor sensitivity to multiple drugs. As part of this pilot study, we have developed and characterized normal iPSCs. After 3 weeks of exposure to GBM microenvironment, we have observed changes in morphology and rate of proliferation in iPSCs. This pilot project is expected to yield novel insights into oncogenesis and lead to novel cancer therapies.
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