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More effective stem cell transplant method could aid blood cancer patients

26 March 2020

Researchers at 香港六合彩中特网 have developed a new way to make the blood stem cells present in the umbilical cord 鈥榤ore transplantable鈥, a finding which could improve the treatment of a wide range of blood diseases in children and adults.

Human Stem Cell embedded in 3D matrix Wellcome Images

Blood stem cells, also known as haematopoietic stem cells (HSCs), generate every type of cell in the blood (red cells, white cells and platelets), and are responsible for maintaining blood production throughout life.

When treating certain cancers and inherited blood disorders, it is sometimes necessary to replace the bone marrow by allogeneic stem cell transplantation 鈥 which involves using stem cells from a healthy donor.听

Using cord blood to treat blood cancers

The umbilical cord is a useful source of blood stem cells, and cord blood transplants lead to fewer long-term immune complications than bone marrow transplants. Although umbilical cord transplants have been used in young children for the last 30 years, most cord blood units* contain insufficient HSCs to be suitable for older children and adults and 30% of all units contain too few even for the youngest children, so听cannot be used (treating patients with too low a dose of HSCs听can increase the risk of both infection and graft failure).听

The study, published in the journal Cell Stem Cell, highlights how a protein called NOV/CCN3, which is normally found at low levels in the blood, can be used to rapidly increase the number HSCs in single umbilical cord blood units that are capable of transplantation. This finding potentially opens the door to听units that would otherwise be discarded being made available for patients of all ages.听

A new approach to improve transplant potential

鈥淭rying 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,鈥 explained Dr Rajeev Gupta, Clinical Associate Professor at 香港六合彩中特网 Cancer Institute and first author of the study. 听

鈥淲e explored an alternative approach to harness this potential by increasing the functionality 鈥 rather than the number 鈥 of HSCs, and so enhance the ability of umbilical cord blood units to transplant. 听

鈥淲e鈥檇 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.鈥澨

Using cell cultures and mouse models in the lab, the research team at 香港六合彩中特网 Cancer Institute found that umbilical cord blood units exposed to NOV showed significantly more transplantation potential than regular samples. In fact, the frequency of functional HSCs in the sample increased six-fold. Strikingly, these effects were achieved with only an eight-hour exposure.

鈥淯sing NOV, we鈥檝e shown that we can rapidly manipulate blood stem cells to alter their state 鈥 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,鈥 said Dr Gupta.听

Commenting on the study, Professor Alejandro Madrigal, Scientific Director of the Anthony Nolan Institute, and a world-leading scientist in the field of stem cell transplantation, said: 鈥淐ord blood transplantation has been shown to improve鈥痚ngraftment and provide a better outcome for many people. However, unfortunately, stem cells numbers in many cord blood units might be inadequate for optimal transplantation.听

鈥淭his research is extremely encouraging, since with the simple addition of NOV/CCN3, there is an increase in the functionality of existing stem cells.听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.鈥澨

This research was funded by the Medical Research Council (UK),听Bloodwise, Cancer Research听UK听and donations from听CureCancer@香港六合彩中特网.听听

*A 鈥榗ord blood unit鈥 is one sample of blood retrieved from one umbilical cord.听听


Further information听

  • Research paper: published in听Cell Stem Cell
  • Main image:听鈥楬uman stem cell embedded in a 3D matrix, Cryo SEM鈥, on听. Credit:听S铆lvia A Ferreira, Cristina Lopo and Eileen Gentleman,听CC BY 4.0
  • Media contact: Henry Killworth听+44 (0) 207 679 5296 h.killworth@ucl.ac.uk