Project V

Sarah Harcum

Improved Reactor Control for Stem Cell Expansion to Meet Therapeutic Needs

Target Investigator
Dr. Sarah Harcum
Associate Professor of Bioengineering
Clemson University

Regenerative medicine-based therapies hold the power to dramatically enhance treatments. At the forefront of regenerative therapies waits the untapped potential of stem cells; however, for stem cell-based therapies to be feasible, the challenge of generating sufficient numbers of undifferentiated stem cells remains.

Twenty years ago, mammalian cell densities of one-half million cells/mL were commonly obtained. Today, researchers routinely achieve cell densities of over ten million cells/mL. Improved control of bioreactors coupled with a deeper understanding of how the bioreactor environment affects cell physiology allowed this improvement. Significantly increasing throughputs and yields for therapeutic stem cell production by improving the robustness of bioreactor controls along with an improved understanding of stem cell physiology in bioreactors remains the long-term goal.

Major transformative changes in bioreactor control to improve the control algorithms include:
1) Develop control software that incorporates cell growth models to estimate growth/proliferation to improve bioreactor throughputs and yields;
2) Develop a bioreactor control system that directly accounts for the known interactions between typical control parameters instead of the independent controls currently used;
3) Develop offline process sampling inputs to the control.

This innovative approach combines current mammalian cell production methods with existing mathematical biological models and real-time parameter estimation into a single robust platform that can greatly improve stem cell yields. To achieve this aim, stem cell growth characteristics in the standard culture setups need to be determined. Characterization of stem cell growth in industrial-like bioreactors using standard control algorithms is needed to culture the stem cells in bioreactors using the model-based control. The growth characteristics and differentiation potential will be compared to the standard growth condition outcomes.

This project will pave the way for future treatments by allowing the generation of adequate amounts of raw materials (stem cells) necessary for feasible regenerative medicine-based therapies.

Please click here for more information about Dr. Harcum's laboratory.