Abstract:
With the goal of screening cells in an environment that mimics that of native tissue, we designed a hydrogel for 3D cell culture. With 3D cell culture, we gain an understanding of both cell invasion and cell viability, thereby providing insight that is inherently unavailable with traditional 2D cell culture. To achieve a suitable environment, we synthesized hyaluronan-based hydrogels because hyaluronan is often over-expressed in invasive tumours including those in the breast and lung [1]. To facilitate cell invasion and remodelling of the matrix, the hydrogels are crosslinked with peptides that can be degraded by matrix metalloproteinases (MMPs) secreted by the cells. To enhance cell adhesion, the hydrogels are modified with proteins and/or peptides; to facilitate cell invasion, the hydrogels are modified with growth factor concentration gradients [2]. Using these well-defined hyaluronan-based hydrogels, we investigate both breast cancer [3] and lung cell [4] invasion and their response to different therapeutic treatments.
Acknowledgments: We are grateful to NSERC and CIHR for funding.
References:
[1] Fisher, S.; Anandakumaran P.; Owen, S.C.; Shoichet, M.S. 2015 “Tuning the microenvironment: click-crosslinked hyaluronic acid based hydrogels provide a platform for studying breast cancer cell invasion”, Advanced Functional Materials, 25: 7163-72; doi: 10.1002/adfm.201502778
[2] Fisher, S.A.; Tam, R.Y.; Fokina, A.; Mahmoodi, M.M.; Distefano, M.D.; Shoichet, M.S. 2018 “Photo-immobilized EGF chemical gradients differentially impact breast cancer cell invasion and drug response in defined 3D hydrogels” Biomaterials, 178: 751-66; doi: 10.1016/j.biomaterials.2018.01.032
[3] Baker, A.E.G.; Bahlmann, L.C.; Tam, R.Y.; Liu, J.C.; Ganesh, A.N.; Mitrousis, N.; Marcellus, R.; Spears, M.; Bartlett, M.S.; Cescon, D.W.; Bader, G.D.; Shoichet, M.S. 2019 “Benchmarking to the gold standard: hyaluronan-oxime hydrogels recapitulate xenograft models with in vitro breast cancer spheroid culture”, Advanced Materials, 31: e1901166; doi: 10.1002/adma.201901166
[4] Tam, R.Y.; Yockell-Lelievre, J.; Smith, L.J.; Julian, L.M.; Choey, C.; Baker, A.E.G.; Hasim, M.S.; Dimitroulakos, J.; Stanford, W.L.; Shoichet, M.S. 2018“Rationally designed 3D hydrogels model invasive lung diseases enabling high-content drug screening”, Advanced Materials, 1806214: 1-9; doi: 10.1002/adma.201806214