Establishing multipotent stem cell lines from CNS tumours
Research type
Research Study
Full title
Establishing multipotent stem cell lines from central nervous system tumours
IRAS ID
206676
Contact name
Hesham Zaki
Contact email
Sponsor organisation
Sheffield Teaching Hospitals NHS Trust
Duration of Study in the UK
1 years, 11 months, 30 days
Research summary
A striking feature of some central nervous system (CNS) tumours is the presence of cell types indicative of mixed neural/glial and mesodermal/mesenchymal (e.g. skeletal/smooth muscle, cartilage, bone) differentiation. These neuromesodermal (NM) tumours are distinct from germ cell-derived pluripotent teratocarcinomas and are classified as variations of a wide spectrum of brain cancers exhibiting diverse histopathological, molecular and age-onset profiles. They are thought to arise from stem cells resembling embryonic precursors which have the capacity to generate both neural and mesodermal lineages. NM tumours are highly aggressive, associated with poor prognosis and are often misdiagnosed using conventional immunohistochemical markers. Thus it is possible that these malignancies are more common than previously thought and understanding their biology is important for the development of improved therapeutic approaches. An attractive strategy for their treatment involves the isolation and culture of tumour-initiating cells which can be used as a target population for drug development. However, there are currently no such cell lines available for NM brain tumours. This is because the conventional route for brain cancer cell line derivation involves the use of culture conditions promoting neural stem cells rather than multipotent cell populations. In this study we propose to establish cell lines from NM CNS tumours by employing conditions we have found to favour precursor populations which occur naturally during early embryogenesis and can generate both neural and mesodermal cells, namely neuromesodermal progenitors or neural crest stem cells. We will also test whether markers of these embryonic populations can be utilised for the immunohistochemical detection of NM brain cancer stem cells in tumour samples. Such NM cancer stem cell lines will be a valuable resource for the scientific community and will serve as an ideal in vitro model for studying the links between embryonic and cancer stem cells.
REC name
Wales REC 7
REC reference
16/WA/0380
Date of REC Opinion
7 Dec 2016
REC opinion
Favourable Opinion