Scientists have developed a method that improves the functionality of cord blood stem cells. A study, conducted on mice, will help improve the quality of treatment for a wide range of blood diseases in children and adults.
Blood stem cells, also known as hematopoietic stem cells (HSCs), generate all types of blood cells (red blood cells, platelets, and various types of white blood cells) and are responsible for maintaining blood production throughout life.
In the treatment of certain types of cancer and hereditary blood diseases, bone marrow replacement is sometimes necessary with allogeneic stem cell transplantation, that means the use of stem cells from a healthy donor.
The umbilical cord is a valuable source of HSCs, and cord blood transplantation leads to fewer long-term immune complications compared to bone marrow transplantation.
Although umbilical cord transplants have been used in young children for the last 30 years, most cord blood units do not contain enough hematopoietic stem cells to treat older children and adults. In addition, about 30% of all units are disposed of because they contain too few HSCs even for the youngest babies.
A study, published in the journal Cell Stem Cell, showed a protein called NOV/CCN3, which is normally found at low levels in the blood, can be used to rapidly increase the amount of HSCs in some units of cord blood.
This discovery potentially allows the successful transplantation of units of cord blood, which otherwise would have been simply disposed of, and makes it accessible to patients of all ages.
“Trying to increase the actual number of hematopoietic stem cells in umbilical cord blood is both expensive and challenging. It is known that not all HSCs present in a cord blood unit can or will transplant, indicating that cord blood units have untapped transplantation potential”, – explained Dr. Rajeev Gupta, Clinical Associate Professor at UCL Cancer Institute and first author of the study.
“We explored an alternative approach to harness this potential by increasing the functionality – rather than the number – of HSCs, and so enhance the ability of umbilical cord blood units to transplant. We’d previously discovered that a regulatory protein known as NOV is essential for the normal function of human HSCs, and so we asked whether highly purified NOV might be used to manipulate cord blood HSCs to make them more transplantable.”
Using cell culture and mouse models in the laboratory, the UCL Cancer Research Institute research team found that cord blood units treated with NOV protein showed significantly greater transplant potential than conventional samples. In fact, the number of functional HSCs in the sample increased sixfold. Amazingly, this effect was achieved only by the eight-hour exposure of NOV to cell culture.
“Using NOV, we’ve shown that we can rapidly manipulate blood stem cells to alter their state – changing non-functioning HSCs to functioning HSCs – which enhances cord blood engraftment potential. This finding offers a new strategy for improving blood transplants. The next stage will be to take our research into a clinical setting to explore how this can benefit patients with blood cancers and other blood disorders”, – said Dr. Gupta.
Commenting on the study, Professor Alejandro Madrigal, research director at the Anthony Nolan Institute and a world-renowned stem cell transplant scientist, said:
“Cord blood transplantation has been shown to improve engraftment and provide a better outcome for many people. However, unfortunately, stem cells numbers in many cord blood units might be inadequate for optimal transplantation. This research is extremely encouraging, since with the simple addition of NOV/CCN3, there is an increase in the functionality of existing stem cells. This practical solution could enable many more cord blood units, which have a limited number of stem cells, to be made available for transplantation and could make a huge difference to the many patients.”