Induced pluripotent stem (iPS) cells hold the potential to drastically improve cell-based therapies in the near future. Yet, in order for stem cell therapies to become clinically feasible, one must be able to generate stem cells in sufficient quantity and maintain pluripotency characteristics.  Rapidly proliferating cells, including induced pluripotent stem (iPS) cells and cancer, consume glucose and secrete lactate at high rates, even in the presence of sufficient oxygen, a process referred to as the Warburg effect.  In cancer cell metabolism, lactate accumulation is associated with cancer stem cell-like gene expression, drug-resistance, metastasis, and poor prognosis in breast cancer patients.  Lactate has also been shown to cause hypoxic gene expression in both tumor and noncancerous cells grown in normoxic conditions. In iPS cells, elevated lactate conditions have been shown to preferentially cause differentiate into cardiomyocytes in glucose-deficient media.  Yet, there remains an incomplete understanding of the role of lactate in stem cell metabolism and pluripotency in glucose containing media.  The overall aim of this work will be to obtain a comprehensive understanding of how environmental conditions affect iPS cell metabolism and pluripotency.  This study specifically examined the impact of extracellular lactate on the metabolic activity and pluripotency in human K3 iPS cells grown in both high and low glucose media.  Extracellular glucose, lactate, and amino acid concentrations were monitored throughout the experiment to quantify the extracellular consumption and production fluxes.  The high extracellular lactate resulted in altered cell metabolism, including decreased lactate production, while glucose consumption remaining unchanged.  These results support the hypothesis that there is redistribution of carbons within metabolism under high extracellular lactate, with a larger portion of carbon entering the tricarboxylic acid (TCA) cycle.  The implications of these findings towards understanding iPS cell metabolism and designing cell culture conditions to limit lactate accumulation will be discussed.<br/>

Evaluating the impact of high extracellular lactate on induced pluripotent stem cell metabolism and pluripotency

253rd National Meeting (2017)

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