Research Project
9162032
Current mechanisms for the expansion of cancer cells result in the diminishment or depletion of the cancer stem cell population due to the necessity for irreducibly complex media additives or the lack of a proper microenvironment. Evidence continues to mount from numerous groups detailing the indispensable role tumor endothelial cells (ECs) have in promoting cancer stem cells proliferation, chemoresistance, and phenotype via the secretion of numerous growth factors, termed angiocrine factors. Traditional mechanisms of culturing endothelial cells have not been permissible to recapitulate the in vivo microenvironment generated by ECs due to phenotypic instability in culture. This limitation has been eliminated in ECs by the VeraVecTM EC platform by the addition of the Ad5 E4ORF1 protein. VeraVecTM ECs have repeatedly demonstrated their capacity to expand cancer stem cells with high fidelity and high engraftability in co-culture conditions. However, large scale co-cultures of cancer stem cells and VeraVecTM ECs are labor intensive, logistically challenging, and consume large quantities of reagents. We therefore propose to introduce the coculture into the TerumoBCT Quantum hollow fiber bioreactor to automate the expansion. The end product will be an automated, large scale, high fidelity expansion without sacrificing any benefits of the VeraVecTM platform.
