Improving embryonic stem cell expansion through the combination of perfusion and Bioprocess model design

PloS One
David YeoA Mantalaris

Abstract

High proliferative and differentiation capacity renders embryonic stem cells (ESCs) a promising cell source for tissue engineering and cell-based therapies. Harnessing their potential, however, requires well-designed, efficient and reproducible expansion and differentiation protocols as well as avoiding hazardous by-products, such as teratoma formation. Traditional, standard culture methodologies are fragmented and limited in their fed-batch feeding strategies that afford a sub-optimal environment for cellular metabolism. Herein, we investigate the impact of metabolic stress as a result of inefficient feeding utilizing a novel perfusion bioreactor and a mathematical model to achieve bioprocess improvement. To characterize nutritional requirements, the expansion of undifferentiated murine ESCs (mESCs) encapsulated in hydrogels was performed in batch and perfusion cultures using bioreactors. Despite sufficient nutrient and growth factor provision, the accumulation of inhibitory metabolites resulted in the unscheduled differentiation of mESCs and a decline in their cell numbers in the batch cultures. In contrast, perfusion cultures maintained metabolite concentration below toxic levels, resulting in the robust expansion (>16-fold)...Continue Reading

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Citations

Mar 22, 2014·Biotechnology Letters·Ailing TeoMayasari Lim
Oct 11, 2014·Expert Opinion on Biological Therapy·Zakareya GamieEleftherios Tsiridis
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Jan 27, 2017·Genes·Alex Vassilev, Melvin L DePamphilis

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Methods Mentioned

BETA
sandwich immunoassay
PCR
flow cytometry
dissection

Software Mentioned

SigmaStat
Olympus
gPROMS®
analysisD

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