Scientists have found a potential new way to increase the supply of stem cells from bone marrow transplant donors.
Currently, donors are often given granulocyte-colony stimulating factor (G-CSF) or Plerixafor (an immune stimulant) to move hematopoietic stem cells from the bone marrow into the blood, so that they can be harvested less invasively.
Scientists led by Dr Yoshio Katayama of Kobe University Hospital, Japan, set out to understand how the mobilisation of stem cells from the bone marrow works. Their findings are published in the journal Blood.
They gave G-CSF to mice in the lab and observed its effects. They found that G-CSF increased the amounts of fibroblast growth factor-23 (FGF23) in the bone marrow, which encourages the mobilisation of haematopoietic stem cells out into the peripheral blood.
The increase in FGF23 was mainly caused by red blood cell precursors, called erythroblasts, in the bone marrow. This was triggered by low oxygen levels in the bone marrow, which is known to be caused by G-CSF treatment.
FGF23 is mostly produced by bone cells, so this new function was previously unknown.
The authors explain that high FGF23 levels in bone marrow cause release of haematopoietic stem cells by suppressing a chemokine receptor, called CXCR4, which would otherwise anchor these cells in the bone marrow.
The team hope their discovery will lead to new strategies for stem cell harvesting. In particular, they hope it will help avoid the insufficient mobilisation that occurs in about 10% of bone marrow transplant donors.
Ishii S, Suzuki T, Wakahashi K, Asada N, Kawano Y, Kawano H, Sada A, Minagawa K, Nakamura Y, Mizuno S, Takahashi S, Matsui T, Katayama Y. (2020) “FGF23 from erythroblasts promotes hematopoietic progenitor mobilization.” Blood, doi: 10.1182/blood.2020007172
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