Canadian scientists have found a new way to prompt haematopoietic stem cells (HSCs) from the bone marrow of mice to multiply, in order to provide a large quantity of HSCs from a small sample of bone marrow. They hope that this technique, if it also works in humans, will provide an alternative and more readily available source of HSCs for use in bone marrow transplants.
The research team from the Institute for Research in Immunology and Cancer (IRIC), Universite de Montreal, screened 700 proteins produced by mouse HSCs to see what effect each protein had on the behaviour and function of the HSCs. They found that ten of these proteins caused the HSCs to divide and that by genetically manipulating HSCs to over-produce these proteins they could encourage cell division and thereby increase their supply of cells. Dr Guy Sauvageau, who led the study, said: 'the next step is to verify whether this also works in humans. Everything is already in place.' These experiments will be performed at the Maisonneuve-Rosemont Hospital in Montreal.
Bone marrow transplants are used to treat individuals with diseases or cancers of the blood such as leukaemia. The patient's bone marrow, which harbours the cancerous cells as well as the HSCs that create new blood cells, is destroyed by radiation and replaced by HSCs from a healthy individual. These healthy HSCs then create new cancer-free blood cells. One limitation of bone marrow transplants is that the recipient and the donor must be matched for a set of genetic markers (known as their 'tissue type') so that the recipient's immune system does not reject the new HSCs. It is not always possible to find a compatible donor.
If it proves to be possible to expand human HSCs in the same way as the mouse HSCs, then it may be possible to create new sources of HSCs. In particular, umbilical cord blood taken at birth contains some HSCs, although not enough for a normal, adult bone marrow transplant. 'If you could increase the stem cell number by two- to three-fold in these units [of cord blood]...that would be sufficient now to transplant a human adult', said Dr Sauvageau. He added: 'If only one of the ten proteins allows HSCs to be multiplied in humans, we will be able to obtain the quantities of cells necessary to perform transplants'. Cord blood is readily available and it is stored around the world in banks that contain samples of every tissue type.
Dr Sauvageau also hopes the method may also have implications for the after care and health of people who receive solid organ transplants. Studies in mice indicate that transplanting donor HSCs at the same time as the organ may help prevent the recipient's immune system rejecting the organ and so reduce the need for drugs to repress the immune system.