Bioprocess development, scale-up and optimization
To accelerate our efforts to produce therapeutic cells such as pancreatic beta cells and endothelial progenitor cells (EPCs), we are developing screening methodologies to systematically optimize cell culture conditions. For example, we have applied statistical design of experiments and high-content imaging to identify compounds that enhance pancreatic duct cell proliferation. Although it is unlikely that duct cells contribute to beta cell regeneration in adults, beta cells arise from progenitors within the duct during development. The duct cells could therefore be reprogrammed to generate beta cells. Other potential beta cell sources are other adult cell types reprogrammed into pluripotent stem cells. Although beta cell progenitors can be efficiently derived in vitro from pluripotent stem cells, obtaining fully mature beta cells in a reproducible manner is challenging. We are developing novel screening tools that could help overcome the last roadblock towards robust production of beta cells from pluripotent stem cells.
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Fekete N, Béland AV, Campbell K, Clark SL, Hoesli CA. (2018) Bags versus flasks: a comparison of cell culture systems for the production of dendritic cell-based immunotherapies. Transfusion. 58(7):1800-1813. doi: 10.1111/trf.14621
Bastien J, Fekete N, Beland AV, Lachambre M-P, Laforte V, Juncker D, Dave V, Roy D-C, Hoesli CA. (2020) Closing the system: production of viral antigen-presenting dendritic cells eliciting specific CD8+ T cell activation in fluorinated ethylene propylene cell culture bags. Journal of Translational Medicine. 18:383. doi: 10.1186/s12967-020-02543-1