Engineered macrophages boost blood cell production

Scientists at CRM have been able to engineer specialised immune cells known as macrophages in the laboratory from stem cells.

Macrophages are specialist cells that support the immune defences of the human body and can support the growth and repair of damaged organs.  One specialist type of macrophage supports the production of red blood cells in the bone marrow.

The team genetically modified stem cells in which a single gene, called KLF1, could be switched on. When the gene was switched on the team were able to produce macrophages that could support red blood cell production.

Mimicking the cell environment

Until now it has not been possible to mimic the cell environment that supports red blood cell production. This is the first time scientists have been able to do this in the lab and it allows them to study the precise details of the process. 

Further investigation of the genes that were switched on or off by KLF1 in macrophages identified three cell products which are important for red cell production. Addition of these factors in combination increased red cell production in the absence of macrophages.

Although this improves red blood cell production in the lab, the team emphasise that we are still a long way from producing enough blood of the right quality for blood transfusions. More significantly, they say, the ability to manipulate macrophages in this way could allow the production of immune cells which could help repair damaged tissue in the human body.

“This work is really exciting because it demonstrates that we can generate a specific type of macrophage in the laboratory.  In this study we make macrophages that improve blood cell production but it could be adapted to make macrophages that do other jobs in the body such as repairing damaged tissue.”

Professor Lesley Forrester

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This work was funded by Wellcome Trust, CONACYT, Wellcome Trust, Medical Research Council and COST Action BM1404 Mye-EUNITER (http://www.mye-euniter.eu). It is published in Nature Communications.

The Forrester group pages

Lopez-Yrigoyen et al (2019). Genetic programming of macrophages generates an in vitro model for the human erythroid island niche. Nature Communications 10:881. https://www.nature.com/articles/s41467-019-08705-0