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Peripheral Blood Mononuclear Cells in Drug Discovery and Development

Jan 14, 2014 7:00:10 AM / by Maria

Use of human samples including peripheral blood mononuclear cells (PBMCs) in drug discovery is critical for increasing the chances of success for a small molecule screen hit. This is the first in a four part series on peripheral blood mononuclear cells and their use in drug discovery.

[pullquote]The path to FDA approval is a long and risky one. It takes about 14 years for one out of 10,000 compounds studied to make it to the clinic.[/pullquote]

Several theories try to explain why many drug discovery and development projects have a very low rate of success. Even with the advances made in methods like high-throughput screening (HTS) that allow for faster, automated testing on a much larger scale (compound libraries of thousands to millions!), there are many hurdles for a small molecule on the long road to FDA approval.

One way that may improve predicted efficacy and toxicity of drug leads is to use human samples such as blood early in drug discovery programs. Peripheral blood mononuclear cells  (PBMCs) can be easily obtained and used in a variety of ways during the drug discovery process to gain a better understanding of the effects of a small molecule.

Drug discovery research aims are often directed toward determining whether or not small molecules affect cell proliferation, viability, and apoptosis. There are related assays available to measure the effects of drug treatment and, especially for researchers that prefer to use human samples, peripheral blood mononuclear cells (PBMCs) are often the cells of choice.

One in vitro cell proliferation assay requires pre-incubation of the PBMCs with the drugs of interest before incubation with antibodies that trigger T lymphocyte proliferation.[1]The EC50 values can then be determined based on percentage of inhibition plotted against compound concentration. Cell viability and apoptosis assays can be used with PBMCs as well to further confirm that the drugs are specifically inhibiting cell proliferation.[1] Frijters, et. al. even used these assays to validate predicted relationships between compounds and cell proliferation.

Previously we discussed how they can be differentiated into many cell types of interest through cellular reprogramming for various other applications!

The next three articles will further highlight several of the ways that PBMCs can be utilized in drug discovery and development processes, starting with Part II, which will provide examples of how PBMCs have already been used to study the response of healthy and infected cells to drug treatment.

Already know of a way you could use peripheral blood mononuclear cells? HemaCare can provide top quality PBMCs in fresh or cryopreserved format!

Drug Discovery and Development Pipeline Drug Discovery and Development Pipeline
Image credit: http://www.ncats.nih.gov/research/reengineering/process.html

References:

[1] Frijters, R. et al. Literature mining for the discovery of hidden connections between drugs, genes and diseases. PLoS Computational Biology 6, no. 9 (2010): e1000943.

Topics: drug screening, Drug Discovery, PBMCs, Peripheral blood cells, Basic Research

Maria

Written by Maria

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