Today we know the function and metabolism of any mammalian cell depends on its environment. Such cells have long been cultivated under conditions consisting of a basal medium with added nutritional serum. However, this is not an exact replica of the environment of cells in the human body.
Now, investigators are thinking about how to make such media more similar to the natural environment of cells that want to grow. New article in the magazine Trends in cell biology in November 2019 describes how physiological media, as they are called, will help to visualize the behavior of cells under natural bodily conditions when exposed to biological agents or drugs.
Asonejon Cantor is a metabolism researcher at the Morgidge Research Institute in Madison and a professor of biochemistry at the University of Wisconsin-Madison. Image Credit: Mortridge Research Institute
The current study is led by Asonesson Cantor, a biochemist who helped develop Human Plasma-like Media (HPLM) in Cambridge. This new medium has been carefully crafted to be just like the plasma of a typical human adult, and is now used in over 30 laboratories to model the response of cells to various substances when introduced into the bloodstream.
Researchers want to examine how different types of human cancer cancers grow and function when grown in HPLM compared to the more common type of medium. The physiological nature of HPLM means that the biology of these cells is more likely to be closely related to the way cells behave in the human body. This will not only help us understand more about how the cells function in real life, but these insights help discover how the drug really affects the cell, how it can be prevented under body conditions, and how it can be improved. Thus, it can have a major impact on drug development and formulation.
Cell culture media
Honestly, until now, all the scientists have wanted in cell culture is that they need to grow as many cells in as little time as possible, and that new cells need to be normal and able to reproduce just like stem cells. However, this setting does not always allow for biological conditions to be simulated, meaning that experiments focusing on how cells behave under different exposures, for example, are not always impermeable.
Much of the biological knowledge comes from living cells grown in a flat dish, in cell culture media composed of selected chemicals and nutrients. This includes mechanical support for cell fixation, as well as physical and chemical parameters such as osmolar, pH and temperature conditions. This setting allows for rapid proliferation and growth of viable cells.
However, traditional culture media consist of a base that is completely unlike anything in the human body, with nutrients added in the form of undefined serum (usually from bovine fetuses or calves) that have no discernible resemblance to human blood or extracellular fluid. . The serum adds growth factors, hormones and trace elements to the mix, which are essential for breeding. However, the fact is that we do not know much about what else can be added to the serum in the culture medium. The result is a medium that is not much like human blood in its metabolic composition.
Avoiding the addition of serum, as an undefined ingredient, is also problematic because it prevents the use of the resulting medium, which must be built with carefully added individual nutrients for more than one or very few cell types. In addition, when these elements, including trace elements, are added to simulate human plasma, there may be a possible overdose of trace metals leading to toxicity or oxidative stress due to the absence of binding or carrier proteins found in the serum. .
Why is serum simply not used? Price is forbidden, for one, along with the innate differences between the batches of different organisms, the compositional complexity and resistance to modulation of one or more factors, without having to change the whole thing around, making this less than ideal solution.
Physiological media for cell culture
Simulating natural physiology is one of the primary goals of many current technologies, including 3D cultures, organ-on-chips, microfluidic culture systems, and hermetically sealed cultures that mimic the interior of a solid tumor without access to oxygen.
The basic goals of classical media and physiological media are quite different. With the former, the focus is on rapid growth and multiplication of viable cells, while physiological media are designed to promote cell growth as closely as possible to real work. Researchers insist that each type of physiological medium should be developed in response to its need to model a particular type of cell or application.
Of course, there are challenges with physiological media. It is difficult to remove fat from this medium, for one, without removing growth factors and hormones at the same time. Second, a direct comparison of the metabolic profiles of cells grown in HPLM and blood extracted cells is impossible because it takes about 10 times longer to simply isolate the latter, compared to the former. However, newer techniques are being developed nowadays to monitor patterns of nutrient utilization within tumors, and they can be tested using the same tumor cells grown in physiological media. This comparison could yield interesting results.
Mouse models are often thought to be closer to human physiology than in vitro studies using cell cultures. However, physiological media have already been shown to affect metabolism in a way that would not be possible with mouse models due to the tenfold difference in the concentration of a particular metabolite, uric acid. This should prompt research to consider how best to utilize and incorporate cell culture in physiological media, as well as mouse models, to learn how cells function in the body.
The implications are huge. Physiological media could be used to generate cultured cells for the production of biomolecules of interest, such as viruses or proteins; develop new mobile lines; to move cells in different directions of development; to understand how different metabolites regulate cell growth and function; and for high-flow genomics, proteomics, and metabolism studies.
In Kantor's words, “In most cases, people use media to make something happen. In our case, we only want to study the biology or efficacy of drugs in conditions that we are more likely to see in the human body. Modeling how a cell behaves is a different line of thinking. “
Rise of the Physiologic Media Cantor, Jason R. Trends in Cell Biology, Volume 29, Issue 11, 854 – 861, https://www.cell.com/trends/cell-biology/fulltext/S0962-8924(19)30145 – X