Tools of the trade: Engineering the Cellular Microenvironment with 3D Culture and Protein Affinity Release
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.
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. Using these well-defined hyaluronan-based hydrogels, we investigate both breast cancer and lung cell invasion and their response to different therapeutic treatments. With the goal of modulating protein release, we designed two strategies - one based on affinity and the other on electrostatic interactions. With protein delivery, we can modulate the cellular response in vivo, which we have been pursuing in applications of stroke and spinal cord injury.
Professor Molly Shoichet holds the Tier 1 Canada Research Chair in Tissue Engineering at the University of Toronto. She served as Ontario's first Chief Scientist in 2018 where she worked to enhance the culture of science. Dr. Shoichet has published over 650 papers, patents and abstracts and has given over 375 lectures worldwide. She currently leads a laboratory of 25 and has graduated 185 researchers. Her research is focused on drug and cell delivery strategies in the central nervous system (brain, spinal cord, retina) and 3D hydrogel culture systems to model cancer. Dr. Shoichet co-founded three spin-off companies, is actively engaged in translational research and science outreach.
Dr. Shoichet is the recipient of many prestigious distinctions and the only person ever to be inducted into all three of Canada's National Academies of Science, Engineering and Health Sciences. In 2018, Professor Shoichet was inducted as an Officer of the Order of Canada and in 2011, she was awarded the Order of Ontario. In 2014, Dr. Shoichet received the University of Toronto's highest distinction, University Professor, which is held by less than 2% of the faculty. Dr. Shoichet was the L'Oreal-UNESCO For Women in Science Laureate for North America in 2015, elected Foreign Member of the US National Academy of Engineering in 2016, and won the Killam Prize in Engineering in 2017. Dr. Shoichet received her SB from the Massachusetts Institute of Technology (1987) and her PhD from the University of Massachusetts, Amherst in Polymer Science and Engineering (1992).