Towards Cost-Efficient Culture of Human Induced Pluripotent Stem Cells in Vertical-Wheel Bioreactors

• Autor(a) principal: Salvador, William Lewis Sullivan Coutinho de Oliveira e Sousa
• Data de Publicação: 2022
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/138625
• topic: Human induced pluripotent stem cells; large-scale expansion of hiPSCs; bioprocess economic modeling; vertical-wheel bioreactors; B8; Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias

Human induced pluripotent stem cells (hiPSCs) have the ability to self-renew and to differentiate into any cell type of the human body. For this reason they possess various promising applications in disease modeling, drug discovery and regenerative medicine. However, these applications require large quantities of hiPSCs, in the range of one to ten billion cells. This work sought to identify and explore strategies with the potential to establish an economically viable bioprocess capable of producing these large quantities of hiPSCs. Vertical-wheel bioreactors (VWBRs) and B8 culture medium are among these strategies. An economic model of a bioprocess envisaging the large-scale expansion of hiPSCs was developed. The model allowed for the confirmation and quantification of the economic impact of the considered strategies. It was observed that the supplementation of the culture medium with dextran sulfate significantly reduced the total bioprocess cost by 38%. The same occurs when low seeding densities are employed, with a reduction of 29%. The use of B8 instead of a commercial medium achieves a reduction of 58% in the best case scenario. At the same time, this work sought to reproduce the B8 formula so that it could be tested jointly with VWBRs. The B8 produced was ineffective at maintaining the viability of hiPSCs, although it did not negatively affect their expression of pluripotency markers. The implementation of the strategies analyzed in this work could contribute towards the establishment of the desired bioprocess, promoting the realization of the predicted applications of hiPSCs.