Protein treatment makes HSCs more transplantable

Researchers from University College London (UK) have caused a six-fold increase in the number of hematopoietic stem cells engrafted into mice with a simple protein treatment.

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Researchers from University College London (UK) have demonstrated an ability to increase the engraftment potential of cord blood hematopoietic stem cells (HSCs) six-fold by treating the cells with a protein known as NOV. The findings, described in Cells Stem Cells, could eventually allow cord blood samples to be utilized more effectively, maximizing the number of patients treated with the limited supply of HSCs.

Cord blood frequently contains insufficient HSCs to reconstitute an adult patient following irradiation or chemotherapy, resulting in the cords often being discarded. This novel treatment could see more cord blood samples reaching a useful threshold.

By treating human umbilical cord HSCs with NOV, the team was able to increase the number of HSCs that were capable of engrafting when transplanted into immune-compromised mice. Notably, the team did not increase the number of HSCs, as defined by flow cytometry, but altered their fitness and ability to engraft in the recipient animal.

"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 Rajeev Gupta, Clinical Associate Professor at University College London Cancer Institute (UK).

NOV, also known as CCN3, is a protein naturally found at low levels within the blood and has a range of functions within the cell. Previously, Gupta and colleagues discovered that NOV was essential for regular HSC function, which raised the question of the impact of excess NOV.

"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," continued Gupta.

It remains to be seen if the treatment can be incorporated in a clinical setting and if the results are replicated in human transplantation.

Sources: Gupta R, Turati V, Brian D et al. 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 (2020) (Epub ahead of print); www.ucl.ac.uk/news/2020/mar/more-effective-stem-cell-transplant-method-could-aid-blood-cancer-patients

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