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Platelet production on large scale steps closer with new stem cell method

  |   Stem Cells   |   No comment

Researchers have taken a significant step toward the mass production of platelets for transfusion. They have found a way to create platelet-producing cells from stem cells faster and more efficiently than before.

 

The study is a major step forward toward the goal to make transfusion blood cells in the laboratory instead of relying solely on donation.

 

Platelets are small, colorless cell fragments whose main function is to interact with clotting proteins to stop or prevent bleeding by forming clots. They are produced in bone marrow by precursor cells called megakaryocytes.

 

The researchers, including a team from the British National Health Service (NHS) and the University of Cambridge in the UK, describe their new method of creating megakaryocytes from stem cells in a paper published in Nature Communications.

 

Senior author Cedric Ghevaert, senior lecturer in transfusion medicine and consultant hematologist at NHS Blood and Transplant at Cambridge, says:

 

“Making megakaryocytes and platelets from stem cells for transfusion has been a long-standing challenge because of the sheer numbers we need to produce to make a single unit for transfusion.”

 

He adds that their study represents “a major step forward towards our goal to one day make blood cells in the laboratory to transfuse to patients.”

 

When patients receive blood, they are given either whole blood or specific components, depending on the condition they are being treated for.

 

Up to four components can be derived from donated blood: red cells, white cells, plasma and platelets. Each component serves a different medical need, allowing several patients to benefit from a single unit of donation.

 

Platelet transfusions are given to patients with life-threatening bleeding due to injury or surgery. They may also be given to patients having treatments for cancer or leukemia, or with blood disorders where they cannot make enough platelets of their own.

 

Study ‘paves way for manufacturing platelets for transfusion’

 

In their paper, the researchers describe a new way of chemically reprogramming human pluripotent stem cells (hPSCs) – called “forward programming” – so that they become megakaryocytes (MKs) a lot faster and more efficiently than previous methods. The researchers note:

 

“Critically, the forward programmed MKs (fopMKs) matured into platelet-producing cells that could be cryopreserved, maintained and amplified in vitro for over 90 days showing an average yield of 200,000 MKs per input hPSC.”

 

The chemical “switches” they used to reprogram the hPSCs use three “transcription” factors: GATA1, FLI1 and TAL1. Transcription factors are proteins that help to regulate gene expression.

 

Previously, attempts to make mature megakaryocytes from hPSCs have used a more laborious approach called “directed differentiation,” which takes longer and yields fewer stable, mature megakaryocytes per hPSC.

 

The researchers note that they now need to improve the laboratory culture systems to enable the next step – production of platelets from the megakaryocytes.

 

Dr. Ghevaert and his team are already developing bioreactors that show promise for scaling up platelet production.

 

Mass production of platelets in the laboratory could overcome not only the difficulties of supply but also lead to a more advanced product that would suit patients of all blood types, carry no risk of infection and could be more effective than platelets recovered from blood.

 

Dr. Edwin Massey, Associate Medical Director for Diagnostic and Therapeutic Services at NHS Blood and Transplant, says that the study paves the way for manufacturing platelets for transfusion, but adds:

 

“It will, however, be many years before a process for the large-scale production of platelets is developed.”

 

NHS Blood and Transplant note that around 60% of platelets go to help treat people with cancer, and expect demand to rise as the population ages.

 

Platelet transfusions are often needed to supplement cancer treatment because the chemotherapy – as well as the disease itself – can damage bone marrow, thereby reducing platelets and increasing the risk of bleeding.

 

Last year, Medical News Today learned how coating drugs in the membranes of platelets could make them more effective against cancer.

 

Written by Catharine Paddock PhD

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