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Scalable and Cell-Friendly Technologies for Cell Manufacturing
Clinical outcomes of cell therapies show their revolutionary potential in treating many diseases, and the cell therapy global market is projected to grow at 36.52% yearly to reach $400 billion in 2020. However, a key impediment to meeting the market expectations is the difficulty to manufacture cells at large-scale with current technologies. Current methods have low productivity and can only produce cells for small patient populations and at high cost. For example, it costs about $800,000 for an autologous induced pluripotent stem cell (iPSC)-derived cellular product. Therefore, there is a critical need for a transformative technology that enables scalable culturing of affordable, safe and potent cells to achieve the promise of cell therapies and regenerative medicine. To address the challenge, we developed a platform technology termed AlgTubes (i.e. alginate hydrogel tube cell culture system). AlgTubes provides cells with a culture microenvironment that is aligned with cells’ physiological needs. With AlgTubes, cells are cultured in microscale alginate hydrogel tubes. Nutrients and metabolic waste can freely diffuse through the hydrogel tube walls. The tubes protect cells from hydrodynamic stresses and allow efficient cellular interactions by directing cell expansion both radially and axially while confining the diameter of cell masses ? 400 ?m to ensure efficient mass transport to all the cells in the tube. AlgTubes design results in a paradigm shift in cell culture efficiency as measured by the following norms: cell viability, growth rate, yield, genetic and phenotype stability, culture consistency, scalability (scale out and up) and productivity. For instance, human pluripotent stem cells (hPSCs) expand ~1000-fold per 10 days per passage to yield ~500 million cells/mL in AlgTubes, while merely expand 4-fold per 4 days to yield ~2 million cells/mL in current stirred tank bioreactors (STR). Moreover, AlgTubes can be used to culture many human cell types such as primary human T cells and primary glioblastoma cancer stem cells (CSCs), all with high efficiency. In addition to AlgTubes system, my dissertation also applied a thermoreversible hydrogel-based cell culture system for production of glioblastoma CSCs and protein-producing cells. Finally, we developed a method for fabricating 3D human tissues from hPSCs.
Li, Qiang, "Scalable and Cell-Friendly Technologies for Cell Manufacturing" (2018). ETD collection for University of Nebraska - Lincoln. AAI10979388.