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.

The journey from monocyte to macrophage

Monocytes are highly plastic, heterogeneous cells that are rapidly recruited to sites of inflammation. Toll-like receptors (TLRs) and scavenger receptors on the cell surface, recognize pathogen-associated molecular patterns (PAMPs) and other foreign substances, and adapt their functional role to these environmental stimuli. One response is to differentiate into tissue-specific macrophages, which then engulf and remove cell debris and PAMPs via acidification.

There is a lot still to be done before we fully understand the physiological roles of the different subtypes of human monocytes. What we do know is that they can have either inflammatory or anti-inflammatory properties, and so differentiate into either inflammatory macrophages or anti-inflammatory macrophages .

Granulocyte-macrophage colony-stimulating factor (GM-CSF), which is produced during an inflammatory response by a variety of cells (including fibroblasts and endothelial cells), leads to monocyte differentiation into inflammatory-macrophages. These macrophages are highly aggressive against foreign substances. However, an increase in macrophage colony-stimulating factor (M-CSF, or CSF-1), which is continuously secreted by cells to regulate the production of monocytes in the body, causes them to differentiate into anti-inflammatory macrophages. These macrophages are involved in wound healing and tissue repair.

Tracing the journey of monocytes to macrophages

Real-time monitoring of monocyte differentiation using the IncuCyte ® live-cell analysis system . Data courtesy of Dr Gillian Lovell and Tim Dale (Essen BioScience, now a Sartorius company).

As such, the analysis of both the presence and volume of monocytes/macrophages in the body at a given timepoint can act as a key indicator of inflammatory disease enabling conditions such cardiovascular disease to be diagnosed quickly and efficiently.

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.

Why are Human iPSC-Derived Macrophages an essential tool for your research?

Our hiPSC-Derived Macrophages arrive at the bench as live cells in 96-well plates, so they are immediately ready to use upon arrival. And, depending on the nature of your research, our hiPSC-Derived Monocytes can also be co-cultured with targeted cells to allow the generation of tissue-specific macrophages.

These features mean that you can use iPSC-Derived Macrophages as a physiologically relevant cell model to reliably recapitulate human disease pathways. This gives researchers an essential toolkit to elucidate the biological underpinnings of a disease and potentially uncover new therapeutic pathways.

To learn more about our iPSC-Derived Macrophages and their potential applications in your research, visit our product page here:

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