Achieving controlled human pluripotent stem cell derivation and expansion using Inter-alpha-Inhibitor with a novel polymer substrate (360G-Wellcome-201457_Z_16_Z)

This project will combine the latest advances in synthetic surfaces with the breakthrough discovery of Inter-alpha-Inhibitor (IalphaI) as a soluble, cell attachment-inducing protein, to provide a simplified and economical culture method for human pluripotent stem cells (hPSCs). The current gold standard for hPSC maintenance in vitro still requires ill-defined components with batch-to-batch variability, such as albumin or matrigel. While these conditions have now been refined to purified recombinant components, their high cost still prohibits the large-scale expansion schemes required for therapies. Synthetic surfaces overcome this problem, they are easy and inexpensive to mass-produce, and most important, their production is flexible enough to easily accommodate variable formats depending on the project requirements. Some synthetic surfaces have already been shown to support human PSC growth and expansion, but they still require high concentrations of albumin and underperform compared to traditional methods. I aim to design a hPSC culture method combining a defined, albumin-free medium with a synthetic surface, describe its biological implications on independent hPSC lines and then translate this method to 3D microcarriers and bioreactor-based large-scale expansion. This project will pave the way to clinically safe hPSC lines and scalable culture conditions to make large-scale stem cell therapy a reality.