30 March 2020

British researchers have developed a new method which could boost transplantation from umbilical cord blood.

Umbilical cord transplants have been used in young children for the last 30 years. However, most cord blood units contain insufficient haematopoietic stem cells (HSCs) to be suitable for older children and adults. Added to that, about 30% of all units contain too few even for the youngest children.

Researchers at University College London have revealed that the protein NOV (also known as CCN3) can be used to quickly increase the number HSCs in single umbilical cord blood units that are capable of engraftment.

Publishing in the journal Cell Stem Cell, the team have so far demonstrated their new technique in mouse xenograft studies.

First author Dr Rajeev Gupta, clinical associate professor at UCL Cancer Institute, said this finding potentially enables the use of units that would otherwise be discarded.

“Trying to increase the actual number of haematopoietic stem cells in umbilical cord blood is both expensive and challenging,” he said.

“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.

“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.”

The researchers used cell cultures and mouse models in the lab to discover that umbilical cord blood units exposed to NOV showed significantly more transplantation potential than regular samples, with the frequency of functional HSCs in the sample increasing six-fold with just eight hours of NOV exposure.

“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,” added Dr Gupta.

Professor Alejandro Madrigal, scientific director of the Anthony Nolan Institute, described the findings as “extremely encouraging”, adding: “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.”

The researchers now hope to take their research into a clinical setting to explore how it can benefit patients with blood cancers and other blood disorders.

Source: Gupta R, Turati V, Brian D, Thrussel C, Wilbourn B, May G, Enver T (2020) “Nov/CCN3 enhances cord blood engraftment by rapidly recruiting latent human stem cell activity”, Cell Stem Cell, doi: 10.1016/j.stem.2020.02.012


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