Tracing the journey of monocytes to macrophages: what does it mean for your research?

The human immune response consists of a complex network of cells working together to identify and destroy foreign substances in the body. Two key players in this response mechanism are: 1) circulating peripheral blood monocytes, the cells first to the site of interest; and 2) macrophages, which arise at the point of injury or infection through differentiation of these monocytes into tissue-specific macrophages. Macrophages are responsible for destroying the foreign body before further infection occurs.

Given their crucial role in the immune response and as indicators of various inflammatory diseases, monocytes and macrophages are vital cells to study for biomedical researchers. Further understanding the behaviours of these cells will not only help to elucidate immunological mechanisms but potentially uncover new compounds to facilitate disease diagnoses.

Below we share the remarkable journey of a monocyte to macrophage as an essential component of the immune response, and explore how you can successfully use monocytes and macrophages in your research.

Accessing monocytes and macrophages for your research

Until recently, macrophages for disease research have only been available from an immortalised cell lines (e.g. THP-1) or from peripheral blood. However, recent advances in stem cell biology have resulted in monocytes and macrophages being derived from human induced pluripotent stem cells (hiPSCs) , enabling researchers to overcome the limitations observed with traditional methods whilst still using a physiologically relevant in vitro model.

For example, commercially available myeloid cell lines are known to display an abnormal karyotype and proliferate in vitro , but as hiPSCs are terminally differentiated they do not proliferate. Obtaining macrophages from blood samples can produce a mixed culture of cells – ultimately resulting in a lower proportion of macrophages. This then requires pooling of donor samples and reduced reproducibility of experiments.

At Axol, we produce a vast array of hiPSC-derived cells for use in drug discovery and disease research , which includes the production of both Human hiPSC-Derived Macrophages and hiPSC-Derived Monocytes . By generating hiPSC-Derived Macrophages from our hiPSC-Derived Monocytes, we can produce much purer, higher yields of macrophages in highly defined, serum-free cultures compared to traditional methods.

On top of this, all our cell lines are produced from one stable donor and so don’t require pooling, meaning that hiPSC-Derived Macrophages offer a much more reproducible and reliable in vitro cell model than immortalised cell lines or peripheral blood macrophages, which will ultimately benefit your research.

Cardiac Arrhythmias

Long QT Syndromes

• Long QT syndromes represent a group of hertiable disorders characterized by an extended QT interval with high incidences of sudden cardiac death.
• LQT1 is caused by mutations in KCNQ1 , LQT2 is caused by hERG protein mutations while LQT3 is caused by gain-of-function mutations in SCN5A.
• A number of studies have been carried out using iPSC-derived cardiomyocytes from LQT1-3 patient sources, which have shown disease-specific abnormalities in culture.
• As an example, Moretti et al. , showed that iPSC-derived cardiomyocytes from LQT1 patients exhibit prolonged action potentials.

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)

• • CPVT is an inherited ion channel disorder associated with sudden cardiac death in children and young adults.
• • Mutations in RYR2 are the predominant cause of the disorder.
• • iPSC-derived cardiomyocytes from CPVT patients in a project completed by Kujal et al., in 2012 had aberrant Ca2+ cycling, thus replicating a key characteristic of the disorder.

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

• ARVC is linked with sudden cardiac death and is associated with mutations in desmosomal proteins.
• Ma et al. , revealed that iPSC-derived cardiomyocytes from ARVC patients recapitulate some of the features of the disease including cellular lipid droplets akin to those observed in biopsies of abnormal tissue.