A paper in Nature Medicine
has been has been heralded as a major advance for bone marrow transplantation, reporting a new way of manipulating cord blood stem cells to expand their numbers without causing differentiation from stem cells into normal blood cells (which are unsuitable for transplantation).
Bone marrow donations are used to treat diseases of the blood cells such as leukaemia; the patient’s own, diseased, bone marrow stem cells (which give rise to blood cells) are artificially destroyed and healthy bone marrow from a tissue-matched donor is transplanted to replace them. The procedure may still fail if the patient’s immune system rejects the transplant.
Stem cells taken from umbilical cord blood are a superior source of tissue because they are much less likely to cause immune rejection. This is why cord blood banking is an important medical advance in recent years (see previous news
). However, the relatively small amount obtained from one cord is not usually enough, and patients need two different samples; even then, limited numbers of cord blood stem cells delays the process of repopulating the patient’s bone marrow and increases the risk of medical complications.
US researchers used a Notch ligand protein to stimulate a signalling pathwa
y that caused both mice and human bone marrow precursor cells to proliferate whilst retaining the ability to give rise to different blood cells [Delaney C et al. (2010) Nat Med. doi:10.1038/nm.2080
]. They were able to generate an approximate 100-fold increase in the number of human bone marrow cells.
To test their function in patients, the researchers gave each of ten child and adult leukaemia patients bone marrow transplants from two cord blood samples. In each case one of the two donor samples had been treated to expand the number of cells. These cells showed a faster ability to repopulate the patient bone marrow compared with the untreated ones.
The authors conclude that Notch signalling has a key regulatory role in haematopoiesis (blood cell formation) and that Notch ligands will be useful improving culture of stem cells in the laboratory prior to cord blood transplantation.
: The researchers note that the next step for this research will be studies to determine whether or not the faster engraftment observed for cord blood cells expanded using their method prior to transplantation also improves patient outcomes – fewer infections, faster recovery and improved survival. However, this initial work is very promising. Perhaps if normal cord blood transplantation from unrelated donors can be made safer and more effective, the controversial practice of private cord blood banking will become less common (see previous news