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For many therapeutic purposes, primary cells are extracted from tissues, isolated, cell culture expanded, formulated, and cryopreserved. Biology limits the number of divisions a non-immortalized cell can undergo and it is frequently assumed that the limitations seen in cell culture expansion reflect such biological limitations. We believe that this is not the case and that cells, during standard cell culture, are exposed to certain detrimental conditions, each of which damages part of the cellular machinery and which, in total, result in cells not reaching their full potential due to the accumulated damage - the result is fewer cells with reduced potency.

 

We believe to have identified cell culture conditions removing such limitations so that a greater number of more active cells can be generated

 

Current media are based on work carried out on tumor cells

At the core of media compositions are developments carried out in the 1950s and 60s using tumor cells and their derived cell lines. Such cell lines are immortal, divide at sometimes staggering rates, exhibit abnormal metabolism and, consequently, adapt quickly to - and survive in what has become standard cell culture conditions.

In contrast, primary cells are not immortal, frequently exhibit a much lower rate of divisions and cannot -and should not- be adapted to particular cell culture conditions. Rather, it is cell culture conditions that should be adapted to primary cells.

 

The key point here is that current cell culture media are based on the use of glucose as the primary energy source and this is partly due to the specific needs of tumor cells which utilize glucose at rates sometimes orders of magnitudes higher than that of non-tumor cells - the Warburg effect. However, outside of the body's protective mechanisms glucose is a fuel with distinct disadvantages: in order to liberate the energy contained in the molecule, it needs to be fully oxidized. This requires that pyruvate molecules generated from glucose enter the Krebs cycle quantitatively so that their carbons are quantitatively oxidized to CO2. However, a significant portion of the pyruvate generated from glucose is converted into lactate and only the remainder can be fully oxidized. Thus, a significant proportion of the energy contained in glucose molecules is lost to lactate which, in addition, poisons cell cultures. To make matters worse, the oxidation of glucose yields large quantities of reactive oxygen species which damage the cellular machinery and, consequently, slow down proliferation and reduce the release of bioactive factors, i.e. the potency of cells.

 

In order to release the full potential of primary cells and their cell culture expansion, we looked for alternative fuels and identified ketone bodies as ideal. Ketone bodies, sometimes described as water soluble lipids, are utilized by the body e.g. during times of starvation and we found, that they are oxidized by primary cells at rates much higher than those of glucose and that the oxidation results in formation of reactive oxygen species much lower than that of glucose.

In short, we identified a novel energy source for cell culture media for the expansion of primary cells which provides much more energy than glucose and much fewer negative side effects.

The benefit will be a much higher cell yield of much more potent cells.

We are looking for partners to co-develop the technology to market-ready level. 

For your ready reference, please see the slide deck linked here:

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