UCL Researchers Increase HSCs in Cord Blood to Improve Transplant Potential

UCL Researchers Increase HSCs in Cord Blood to Improve Transplant Potential

Hematopoietic stem cells (HSCs), also known as blood stem cells, are capable of differentiating into every type of blood cell and are essential for maintaining blood production. Blood stem cells are often transplanted into patients who undergo treatment for cancer and for treating individuals with blood disorders.

Blood stem cells are obtained from healthy donors and transplanted, either through an allogeneic stem cell transplant to replace bone marrow or potentially, using an umbilical cord blood transplant. The former carries an increased risk of complications, while the latter is usually safer.

Blood stem cells obtained from the umbilical cord of a donor is a better option; however, transplants of cord blood may not be effective as the number of HSCs in cord blood tends to be low. This approach is usually only useful for treating young children. Many cord blood units also have to be discarded, as they do not contain enough HSCs even for treating young children.

Researchers at University College London have made a discovery that could make cord blood stem cell transplants effective for a much wider range of patients and reduce wastage. The researchers discovered the protein NOV/CCN3 can be used to increase the number of HSCs in single umbilical cord blood units.

“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,” said Dr. Rajeev Gupta, Clinical Associate Professor at UCL Cancer Institute and first author of the study.

The researchers had previously determined the NOV regulatory protein was essential for the normal function of HSCs and investigated whether highly purified NOV could be used to artificially manipulate cord blood HSCs to make them more transplantable.

NOV/CCN3 is usually only found in low levels in the blood. By increasing the level of NOV/CCN3 in cord blood units, the researchers found the transplantation potential increased six-fold in just an 8-hour period. Exposure to the purified NOV changed the state of non-functioning HSCs and made them functional HSCs, thereby increasing the potential for use in cord blood transplants.

The researchers used mouse models and cell cultures in the lab for their research. The next stage is to use the same techniques in a clinical setting to explore whether there is potential for using this approach on patients with blood cancers and other blood disorders.

You can read more about the research in the paper – Nov/CCN3 Enhances Cord Blood Engraftment by Rapidly Recruiting Latent Human Stem Cell Activity – which was recently published in the journal Cell Stem Cell. DOI: 10.1016/j.stem.2020.02.012

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