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Drug Screening in Healthy and Diseased PBMCs

Jan 22, 2014 2:32:37 PM / by Maria

Drug screening can identify therapies for inflammation linked to a variety of diseasesPeripheral Blood Mononuclear Cells (PBMCs) can be used in drug screening.  In Part I from this series, we discussed how they can be used to assay drug activity including effects on proliferation, viability, apoptosis, inflammation, and migration in healthy and disease cell models.  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 are often the cells of choice (PBMCs) are often the cells of choice.  The advantages of using human cells initially are immense.

A biological response that may be of interest in drug discovery is inflammation, which is directly involved in several major diseases ranging from cancer to neurodegenerative and cardiovascular disorders.  PBMCs can also be used in drug screening assays to measure pro-inflammatory activity of small molecules.  Neopterin and tryptophan degradation, markers for immune system activation and inflammation, can be determined in PBMCs by ELISA and HPLC, respectively.[1]

Drug screening can identify therapies for inflammation linked to a variety of diseases.
Image credit: Pan,et al. Food & Function. 2010. 1:15-31.

As a proof of concept, researchers induced inflammation in peripheral blood mononuclear cells and then applied compounds known to reduce inflammation and measured response.  Briefly, the screening was performed as follows:

  • Peripheral blood mononuclear cells were isolated from healthy donors.  (Rather than go to the trouble of recruiting donors yourself - simply order your PBMCs from HemaCare!)
  • Peripheral blood mononuclear cells were activated by addition of the mitogens phytohaemagglutinin (PHA) or concanavalin A (Con A).  This results in neopterin  production and tryptophan degradation.  Both hallmarks of immune response and are associated with increased risk of cardiovascular and neurodegenerative diseases.
  • A series of compounds with known and putative anti-inflammatory properties were added to the activated peripheral blood mononuclear cells.  Compounds screened included cytokines, immunosuppressant drugs, antioxidants, plant extracts, and red and white wine.
  • Canonical measurements of inflammation were analyzed by ELISA and HPLC.

The results demonstrated that drug screening using peripheral blood cells can identify compounds that ameliorate inflammatory response.  Use of primary human cells in compound screening will likely streamline drug discovery by indentifying compounds that will work in human cells.

Primary human peripheral blood mononuclear or monocyte-derived macrophages can also be used in drug screening to identify treatment for infectious diseases. In a simple, inexpensive method, these cells are infected with the bacteria and/or virus. Then drug activity and cell viability can be measured within these in vitro models of infection or co-infection.[2]

PBMCs can also be used to evaluate almost any cellular readout measured in drug screening and provide an ideal primary human sample to be used in drug development.   HemaCare is a leading provider of PBMCs and all of your blood product needs.  In fact, HemaCare cells have been used to develop clinical biomarkers for allograft success demonstrating our quality!   In Part III of this series we discuss how peripheral blood mononuclear cells are advancing cancer therapeutic research.

 

References:

[1] Jenny, M., et al. In vitro testing for anti-inflammatory properties of compounds employing peripheral blood mononuclear cells freshly isolated from healthy donors. Inflammation Research 60, no. 2 (2011): 127-135.

[2] Vijayakumar, S. et al. In vitro model of mycobacteria and HIV-1 co-infection for drug discovery. Tuberculosis 93 (2013): S66-S70.

Topics: drug screening, PBCs, proliferation, apoptosis, Drug Discovery, infection, Inflammation, migration, PBMCs, Peripheral blood cells, viability, Basic Research

Maria

Written by Maria

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