'Step forward' in battle against blood disorders


British scientists have taken a first step towards mass-producing platelets - tiny cell fragments that play a vital role in blood clotting - tailored to individual patients.

The team, including researchers from the NHS organisation responsible for blood transfusions, transformed stem cells into the large bone marrow cells called megakaryocytes that act as platelet factories.

Hundreds of thousands of mature megakaryocytes were produced, which spontaneously began to release functional platelets.

In future, the technique could lead to patients with severe injuries or blood disorders being treated with platelets made in the laboratory from their own cells.

This would overcome a major problem associated with platelet donation, rejection by the recipient's immune system.

Dr Cedric Ghevaert, a leading member of the team from NHS Blood and Transplant, said: "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.

"We have found a way to 'rewire' the stem cells to make them become megakaryocytes a lot faster and more efficiently. It is a major step forward towards our goal to one day make blood cells in the laboratory to transfuse to patients."

Megakaryocytes, unusually large bone marrow cells, are a wonder of biology whose functioning is still not completely understood.

They literally act as platelet factories, generating assembly lines for manufacturing the clotting agents along finger-like branching processes.

Each megakaryocyte churns out between 5,000 and 10,000 platelets - and every adult human has nearly a trillion platelets circulating in their blood.

Platelet transfusions are needed by patients with life-threatening bleeding due to major injury or surgery.

They are also required by people undergoing cancer treatment and individuals with severe blood disorders who cannot make enough platelets of their own.

But patients undergoing multiple transfusions may develop an immune reaction that destroys any "foreign" platelets before they have a chance to do their job. This is especially a problem when a patient is from a minority ethnic group or has a rare blood type.

The megakaryocytes made by the NHS Blood and Transplant and Cambridge University team were derived from cultured lines of embryonic stem (ES) cells and induced pluripotent stem (iPS) cells.

Both are capable of transforming into any kind of tissue in the body. While ES cells are initially obtained from early stage embryos, iPS cells are created in the laboratory from modified adult cells, such as skin cells.  

Mature cells made using the iPS route could theoretically be generated from a patient's own tissue, thereby averting the risk of immune system rejection.

By genetically altering the stem cells in a precise way, the scientists coaxed them into following a development path that led them to multiply and become mature megakaryocytes.

Crucially the process allowed large numbers of the cells to be generated, each stem cell giving rise to some 200,000 megakaryocytes.

The scientists, whose research is reported in the journal Nature Communications, calculated that one million starter stem cells could yield enough platelets for several transfusions.

Next the scientists want to investigate  more efficient ways of producing platelets from stem cell-derived megakaryocytes.

One avenue of research being explored is developing customised bio-reactors that can be used to scale up platelet manufacture.

Dr Edwin Massey, associate medical director for diagnostic and therapeutic services at NHS Blood and Transplant, said: "The success of this research team in producing megakaryocytes in the laboratory has paved the way for the ultimate goal, manufacturing platelets for transfusion. It will, however be many years before a process for the large-scale production of platelets is developed.

"Donated platelets will still be needed by patients for the foreseeable future, either as part of a blood donation or by dedicated platelet donation using a machine collection process."

NHS Blood and Transplant currently collects donated platelets using a machine collection process from 23 donor centres across England.

There is a particular need for "universal" donors who have A negative and AB negative blood groups, as their platelets are compatible with anyone.