High-throughput stem cell bioprocess design - environmental influences on pluripotent stem cell expansion and differentiation

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Regenerative medicine is a rapidly growing billion dollar multidisciplinary field at the intersection of medicine, engineering and science. It aims to create living, functional tissues that can repair or replace damaged, diseased or aging tissues or organs. Stem cells are critical to the success of regenerative medicine therapies, and what are needed are technologies to bridge the gap between basic biology and the clinical application of stem cells. The proposed research program will accelerate the development of these technologies, specifically targeting a reliable, reproducible way to grow stem cells to build tissues. The research will focus on pluripotent stem cells as they have the potential to generate any cell type in the body, i.e. large numbers of specialized (differentiated) cells. They can be derived from the inner cell mass of an early development blastocyst (embryonic stem cells) or from adult cells such as skin cells that are modified by the addition of key factors to be pluripotent (induced pluripotent stem cells). One of the major stumbling blocks on the road to effective regenerative medicine treatments is the limited number of available donor cells, and the small-scale, labour-intensive methods for culturing and differentiating them. The primary objective of the proposed research is to develop engineering methods and technology for efficiently growing human pluripotent stem cells in computer-controlled bioreactors. First, the effect of key bioreactor conditions (such as oxygen level) and the transport of nutrients will be examined for individual stem cell clusters and entire bioreactors. Second, new technology will be developed to accelerate the development of bioprocesses through the use of multiple smaller bioreactors as high-throughput tools to study many conditions quickly. The long term outcomes include innovative bioprocess designs, as well as critical knowledge of how output parameters (i.e. cell type, behaviour) are influenced by cell processing parameters (i.e. bioreactor oxygen level). This is fundamentally necessary for the regulatory approval and clinical application of stem cell technologies, including the generation and transplantation of cells/tissues for the treatment of human ailments (i.e. stroke, Parkinson's disease, diabetes).