‘Supercharged’ blood?

Human blood with red blood cells, T cells (orange) and platelets (green) -

Human blood with red blood cells, T cells (orange) and platelets (green) – this image is by ZEISS MICROSCOPY, licensed under CC-BY-NC-ND 2.0

Cambridge researchers recently moved closer to mass-production of platelets – tiny blood cells with vital roles throughout the body. This ‘forward programming’ method was reported in the journal Nature Communications. This work could result in changes to many lives, enhancing current options in transfusion medicine.  

Meet the platelets

Platelets are involved in many phenomena in the body, from clotting blood to repairing tissue after injury. Once these tiny messengers are activated, downstream events allow formation of a blood clot. This is excellent news most of the time, as this stops you from bleeding to death*.

Normally, 100,000,000,000 platelets are made each day in the bone marrow. But for those with rare platelet disorders, platelet transfusions are a life-line. There are some complications associated with transfusion; one such issue includes short shelf-life – platelets ‘go off’ quicker than most things in your fridge! A stock of lab-made platelets for safe storage and patient transfusion would be excellent news for those with platelet disorders, as well as the wider public.

Around one-quarter of us will need a blood transfusion at some point in our lives, whether that be after giving birth, post-surgery or after receiving various medical treatments. Yet there is a constant issue with supply and demand. It is estimated that only around three percent of eligible donors donate**. These issues all present an interesting challenge for researchers and make this ‘forward programming’ work an exciting possible option for medicine in years to come.

How it works

The Ghevaert group have developed a ‘forward programming’ approach in the lab. This effectively pushes induced pluripotent stem cells (derived from patient skin cells ‘rewound’ to a stem cell fate) towards a megakaryocyte (platelet ‘factory’) cell fate, using a mix of just three different different transcription factors in culture. To quote group leader Dr Ghevaert, ‘We have found a way to “rewire” the stem cells to make them become megakaryocytes a lot faster and more efficiently.’

Of the platelets produced in this ‘forward programming’ process, only around a third of them are functional (their function is gauged in assays that assess factors such as cell shape, spreading and migration). Hence work is underway to create bioreactors that can mimic the bone marrow niche, where platelets are normally produced – thus allowing a higher number of truly functional platelets to be pumped out for future transfusion. Apart from the quality of the platelets produced, another issue is that of further increasing yield. Dr Ghevaert has stated that “the next big step is to get enough platelets out of each megakaryocyte”.

‘Supercharging’ potential?

One day scientists may be able to routinely make blood cells in the lab. What about ‘supercharging’ blood cells prior to transfusion, so they are more effective in repairing damage in the body? This might sound like science fiction, but preliminary efforts in this vein (ahem) are underway, also involving work with platelets.

Platelets are tiny cells, but are nevertheless packed full of proteins: their ‘granule’ structures may carry around 300 different proteins. These proteins are released where needed in the body and play roles in myriad processes, including formation of new blood vessels, inflammation and blood clotting. These granules present an intriguing possibility. Instead of systemically infusing (for example) clotting factors into a patient to treat haemophilia or post-surgical bleeding, we could infuse ‘supercharged’ platelets, to act as a possible specialised tool. These would have the advantage of selectively homing into the site of injury before ‘degranulation’ – release of their protein parcels.

In summary, platelets are small cells, but they pack a big punch. Generation of these cells in the lab represents an exciting step for transfusion medicine, as well as a possible route towards more personalised patient treatments in various avenues of cardiovascular medicine.

S.

platelet forming megakaryocyte* Clotting in the wrong place at the wrong time – thrombosis – can be lethal.

** What are you waiting for?! Look up your local blood donation centre to see if you are eligible to save lives. (Free tea and biscuits included).

Paper reference: Moreau, T. et al. Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming. Nat. Commun. 7:11208 doi: 10.1038/ncomms11208 (2016).

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