Recapitulating the adult stem cell and cancer stem cell niche in vitro using 3D engineered matrices

Breast cancer is a prevalent heterogeneous disease that may have multiple cells-of-origin requiring specific therapeutic strategies. Experimentation to uncover the cell signalling and molecular deregulation in cancer, together with pharmacological drug testing remain highly dependent on the generation of large numbers of specific in vivo animal models. Stem cells, characterised by their proliferative and self-renewal capacity, have been implicated as key players in cancer development, however cancer stem cells and the cell-of-origin remain distinct concepts.

Stem cells reside within a niche, which provides instructive signals in the form of cell-derived soluble factors, cell-cell contacts and extracellular matrix within a 3-dimensional environment. To recapitulate this niche in vitro, we envisage a tissue engineering approach to be necessary, seeding multiple cell types of murine and animal origin into biomaterial scaffolds with controlled biochemical and physical parameters. This project encompasses the development, characterization and validation of a fully humanized tissue analogue of breast.

The development of such a system could greatly enhance research into normal and cancer stem cells and studies of tumour initiation and progression, as well as providing potent therapeutic research tools. Furthermore, the availability of robust, replicable 3-dimensional niche culture models could result in the replacement of animals for stem cell research and ultimately reduce the numbers of animals used for preliminary drug screening, as efficacy on cancer stem cells could be readily assessed.

Hume RD et al. (2018). Tumour cell invasiveness and response to chemotherapeutics in adipocyte invested 3D engineered anisotropic collagen scaffolds. Scientific Reports 8(1):12658. doi: 10.1038/s41598-018-30107-3

Campbell JJ et al. (2017). Development of three-dimensional collagen scaffolds with controlled architecture for cell migration studies using breast cancer cell lines. Biomaterials 114(34-43). doi: 10.1016/j.biomaterials.2016.10.048

Campbell JJ et al. (2014). A 3-D in vitro co-culture model of mammary gland involution. Integr Biol (Camb) 6(6):618-26. doi: 10.1039/c3ib40257f

Campbell JJ et al. (2014). Engineering mammary gland in vitro models for cancer diagnostics and therapy. Molecular Pharmaceutics 11(7):1971-81. doi: 10.1021/mp500121c

Back to top
PhD Studentship

Status

Closed

Principal investigator

Professor Christine Watson

Institution

University of Cambridge

Grant reference number

NC/K001655/1

Award date

Oct 2013 - Mar 2017

Grant amount

£90,000