Microtissue Optimization for Practical Cell-Based Therapies

Substantial resources have been employed in establishing sources of transplantable material for cell-based therapies for various conditions. Many published protocols remain either in the proof-of-concept stage – where the desired cell types can be generated, but in very limited numbers; or scalable, but with low overall efficiency. While illustrative of the tremendous potential of this area of research, in either of these cases significant challenges remain to be overcome in order to deliver a practical, economically viable cell-based therapy to the clinic.

Our research makes use of a microscale-tissue engineering platform technology which we developed, employing uniform size-controlled microtissues to provide a consistent cellular microenvironment. Building on this platform, we are establishing ways of systematically optimizing the production and / or assembly of cells to perform a given function. We were previously able to obtain a 36-fold increase in the yield of definitive endoderm cells from human pluripotent stem cells. I will present our current research, incorporating statistical Design of Experiments and Response Surface Methodology (DOE / RSM) into a generalizable approach for the optimization of cell production from pluripotent stem cells; and also the preparation of functional microtissues for therapeutic use. We have demonstrated the effectiveness of this approach both in vitro and in vivo, and propose that it should be considered by researchers envisaging future cell-based therapies as an outcome of their work.