Certain polymers, especially poly- and oligothiophenes, have been shown to be able to cross cell membranes without additional reagents and to illuminate when interacting with certain structures. For example, it has been shown that certain polythiophenes can cross cell membranes of neurons and illuminate when interacting with amyloid structures from a diversity of proteins, including amyloid-ß and prion. Such polythiophenes are currently under development for early detection of Alzheimer’s disease among other clinical issues.
We initially hypothesized that we could develop similar molecules that based on chemical and structural characteristics could detect and thus be used as markers for various types of stem cells, with the future possibility of using such markers for manipulating the detected cells.
We have tested numerous poly- and oligothiophenes of different length, structure and general characteristics, to see whether these could be used for detection of on one hand “healthy” neural stem cells and, possibly, cancer stem cells, primarily but not exclusively in neural tumors. One of these, an oligothiophene derivative that is the main subject for this application, was identified to specifically detect embryonic neural stem cells in vitro and in vivo histologically, and stem cell-like cells from gliomas in vitro. We named this molecule GlioStem.
The structure of GlioStem with its imidazole rings mimics a histidine/histamine molecule. We have noticed that a key feature for it to function is that GlioStem needs to be methylated, which we have shown is critical for its specificity and function (Figures to be delivered). We have further found that GlioStem detects neural and glioma-derived progenitors in a more specific and sensitive manner than current methods and does not cross-react with any other cell type investigated. The cell types tested include differentiated neural cells (neurons of different phenotype, astrocytes, oligodendrocytes), various fibroblasts, embryonic stem (ES) cells, multipotent stromal cells (also referred to as mesenchymal stem cells), a large number of tumor cell lines of different origin etc.