Last week, Thermo Fisher Scientific presented their third annual 24 Hours of Stem Cells, an innovative virtual conference covering many stem cell related topics, presented by Stem Cell Researchers. The conference materials will remain accessible through March 3, 2016, so you can still check out the presentation topics and speakers. Attendees are able to access a virtual conference hall with several options to explore, including an Exhibit Hall, Resource Center, Virtual Lab and Live and On Demand Presentations.

I attended several of the presentations and I have outlined a few of the talks below:

Biomaterials for Assembly of Stem Cell Derived Human Tissues by Bill Murphy Ph.D., Harvey D. Spangler Professor, Co-Director Stem Cell and Regenerative Medicine, Director EPA Human MAPs Center, University of Wisconsin

Dr. Murphy presented a very interesting keynote on his group’s work in developing Human Models for Analysis of Pathways (Human MAPs). These models will aid in drug discovery, toxicity screening and disease modeling and will provide an opportunity to use human cells and tissues early in the process rather than starting with rodent cells and tissues. Dr. Murphy begins his talk with a very interesting discussion about various synthetic material conditions and the impact they have on cells. One of the first steps that Dr. Murphy describes in the development of Human MAPS was the desire to remove Matrigel due to the large number of proteins present and replace it with synthetic material where the impact to cells could be more accurately predicted and controlled. They began by screening over 500 material conditions looking for “hits” or conditions that would induce assembly of endothelial cells into networks and maintain networks for 48 hours in culture. Dr. Murphy went on to describe one of their projects where they employed this strategy to use high throughput screening for vascular disrupting compounds (angiogenesis inhibitors). What they found was the synthetic material they had identified was more sensitive to identifying these compounds than Matrigel.

I was very interested in another project that his team is working on, which is screening for toxicity to the developing human brain. In this project a multi-disciplinary team worked to assemble brain mimics using synthetic materials and human pluripotent stem cells to produce stratified neural epithelial tissues with vascular networks embedded in them. The idea was to create a drug toxicity prediction model. In this model one could take a compound where toxicity was unknown, then expose the brain mimics to the compound and use a developed algorithm to predict whether the compound was toxic or not. They were able to form neural constructs with high sample uniformity.

Once ready to take the tissues through predictive screening, they began with 60 training compounds (34 know toxins/26 controls). They fed these testing compounds into a machine learning algorithm and were able to achieve 90% accuracy in predictive screening with the training compounds. Then they tested 10 blinded compounds (5 toxins/5 control) and were able to correctly predict 9/10. What they have developed is a system that is quite predictive and superior to previous models. They are planning improvements and are working with the Environmental Protection Agency (EPA) and the National Institutes of Health (NIH) to take the project further and develop an automated high throughput system. There have also been several other Human MAP projects launched including ones to look at cancer, the liver, the eye, the peripheral nervous system, and others.

Generation of Patient Specific iPSC Lines and Scalable Production of PSC-derived Cardiomyocytes, Emily Titus, Ph.D., Manager, Technology, Centre for Commercialization of Regenerative Medicine

Dr. Emily Titus began her presentation with an overview of the Centre for Commercialization of Regenerative medicine (CCRM) and their current work. She began her talk by discussing some of the technical challenges facing the application of pluripotent stem cells and how the Centre is working to provide solutions to these challenges. One step they have taken is to establish an iPSC facility that specializes in reprogramming using non-integrative iPSC generation from various cell sources. They offer contract reprogramming services which can be conducted in about four months and includes assisting with proper sampling techniques, continues to reprograming, expansion and banking followed by extensive characterization and lastly release of frozen vials of cells along with supporting clients as they thaw and culture cells in their own lab. They have also begun including projects, which include gene correction using CRISPR/Cas9.

In addition to their contract reprogramming work, they have also done extensive work to develop a scalable production system for the culture of iPSCs. Their goal was to develop and characterize an efficient, consistent and scalable aggregate-based hPSC manufacturing process in a stirred tank reactor system. They determined that it was important to move to agitated suspension and away from static culture for larger scale production. This was based primarily on the advantages that suspension reactor culture offers including more control of the culture through control of culture factors like dissolved oxygen, pH, temperature, metabolites and feeding. They found they could maximize cell density, culture homogeneity, process efficiency and cell yield. Part of their system includes the use of the AMBR Microbioreactor that allows them to run 25 x 15 ml samples simultaneously to test various culture conditions and a large number of culture parameters using only a small volume.

CCRM then developed a process for translation, scale up and production of PSC derived cardiomyocytes. Their goal was to couple PSC expansion with reproducible, scalable, efficient, cost effective method for cardiomyocyte production. This coupling provided a cost advantage with over 1 billion cardiomyocytes produced in one 12 day run (720 ml). They believe this system is translatable to multiple pluripotent lines and are developing a process to differentiate iPSCs in a similar process.

Essential 8™ Flex Medium Eliminating Daily Feeding in a Feeder-free, Xeno-free PSC Culture System, Matthew Dallas, Staff Scientist, Thermo Fisher Scientific