How Cell-Based Assays are Used in Translational Medicine Studies?

What are Cell-Based Assays?

Assays are basically tests to determine the composition of a substance. And bioassays, quite naturally, are assays that are used to determine how much of a particular substance is present within a sample. Cell-based assays are a kind of bioassay that lets us know the effects of certain substances on a cell population. As you might have guessed from the definition already, cell-based assays are extremely important in the process of drug development.

Previously, there was no way for scientists to be sure about which substance would work well to solve a certain ailment. Drug creations were mostly accidental like Alexander Flemming’s discovery of penicillin. The problem with this process is that drug developers cannot keep waiting for fortunate discoveries to happen. Therefore, there is a need to find substances that can potentially be useful as medicines and then test their medicinal capability. This is exactly what a cell-based assay allows scientists to do now.

However, there is another challenge that needs to be confronted in cell-based assays. How to accurately mimic the physiological setting of a human body so that the safety profile and the action progression of the drug can be tested?

Cell-based assays offer you an ideal solution to this. It is possible to mimic the in vivo conditions in an in vitro setting by recreating the basic components of the original physiological setting of the human body.

What are Cell-Based Assays Used For?

Well, they are used for almost everything- measuring the toxicity of a substance, determining how the cells are dying because of the substance so that a solution to cell death can be found, checking the possibility of cell regeneration, and much more.

Also, you must remember that it’s not enough to discover the medicinal value of a substance. The scientist must also know at exactly which dosage the medicine works best. This is also something that you can find out through particular kinds of cell-based assays. Sometimes, a substance that is not originally toxic, becomes toxic when the dosage is changed. Or, there are even various off-target effects that can only be found out when these experiments are run. All of these factors make these assays a crucial part of drug development.

Why is it Important to Start from the Cellular Level?

There is another key reason why the cell is the key setting where all bioassays should ideally start from. Before you move on to the tissue or muscular level, it is important to understand how a molecule or a compound affects a single cell. This is because once you are in the in vivo level of experimentation, it is too late to make significant changes to the drug. The whole process might have to be redone from scratch if something goes wrong at a later level. To prevent the loss of time, money, and, most importantly, effort, it is crucial that the “trial and error” part of the experiment is restricted to the cellular stage. Yes, before the drug reaches the market, several other rounds of testing are carried out. But these later stages of testing would prove to be completely futile if the data from the initial stages did not exist.

Cell Proliferation and Cell Apoptosis Assays

A certain substance can cause both cell proliferation, that is, regeneration, and cell apoptosis, that is, cell death. Either can be the aim of a drug development project. If the aim is to grow more cells, cell enumeration followed by cell cycle analysis is conducted. Cell division can be measured with the aid of luminescent or fluorescent probes. If cell death is the aim (for example, in the case of cancer research), cell assays that are aimed at identifying apoptotic pathways are used. Also, in cell death assays it is necessary to distinguish apoptosis from neurosis. All of these assays are measured on either flow cytometers or plate readers, or even western blotting.

Potency Assays

Potency Assays are a kind of cell-based assay that lets you know the relative potency of a lot of different batches of a particular drug. This is done to support a lot of releases during the manufacturing process. Potency assays measure the specific events that take place inside the cell when the drug starts acting upon it. These assays are mostly used to prove the reproducibility of a particular drug. But you must keep in mind that only CMP-certified laboratories are allowed to run these assays.

Immunogenicity Assays

The immunogenicity of drugs is also measured through cell-based assays. As you know already, some people have immune systems that immediately react to some unknown drugs because they treat these as antigens. While this reaction can definitely not be compared to an autoimmune disorder, the body does neutralize the effect of the drug. That is, the body forms some anti-drug antibodies (ADAs in short) that bind with the drug (that they have mistaken for an antigen) and prevent it from having any positive effects. In such cases, a cell sample from the patient is specifically tested for these anti-drug antibodies (also known as neutralizing antibodies or NAbs). If these are present, the assay produces a NAb-positive signal. In that case, the doctor is informed that the particular drug cannot be used by the patient.

In Conclusion

Cell-based assays are of various kinds, as has been mentioned in this article. Which one you should use will depend on the end goal of your experiment. Without these assays, there is no sure-shot way of testing potentially beneficial drug leads and coming up with a desirable product that can be released into the market within a short period of time.

Fortuitous discoveries, of course, do keep happening in the medical world. However, the aim is to run these lucky discoveries through several rounds of testing before releasing them to the world. This has to be done to eliminate any possibility of error. Also, it’s not enough to know whether a substance is useful or not. It must also be found out at which concentration the substance is most useful and whether it can work for everyone or produce problems elsewhere in the body. The cell-based assay is the only answer to all of the above problems.