Editors' ChoiceTransplantation

A wealth of cells

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Science Translational Medicine  27 Jan 2016:
Vol. 8, Issue 323, pp. 323ec14
DOI: 10.1126/scitranslmed.aaf0866

Hematopoetic stem cells are the gold standard in cancer treatment, but mining them from bone marrow is difficult and dangerous. Therefore, researchers have turned from invasive bone marrow aspiration to a new mine—umbilical cord blood (UCB). UCB is typically discarded but has been found to be a great source of stem cells that can be used in mismatched settings with improved safety. However, a challenge exists in that the numbers of stem cells in UCB are very low. Doctors have responded to the lack of stem cells in UCB by pooling multiple cords for adult transplants, a costly and complex process. Now, Wagner Jr. et al. may have found a way to perform alchemy. The researchers designed a way to expand stem cells into transplant units that are as safe as, and perhaps more effective than, the current double UCB transplant, potentially obviating the need for pooling umbilical cords and thereby expanding the donor pool of these lifesaving blood treatments.

The expansion works primarily by treating UCB with the aryl hydrocarbon antagonist StemRegenin-1 (SR-1), which increases the number of hematopoietic stem and progenitor cells in a cord. Here, in keeping with the standard double UCB control, 17 patients with leukemia or advanced myelodysplastic syndrome received one unmanipulated unit and one selected for ex vivo expansion culture. Results showed the modified transplants were as safe as the controls: Graft-versus-host-disease (GVHD), transplant-related mortality and overall survival all met historical norms. In fact, post-transplant hospital stays were reduced to 30 days from the historical average of 46.

The process was not just as safe as traditional double UCB transplants, but seemingly more effective. The stem cell expansion worked. The SR-1 expansion cultures increased the number of total nucleated cells 854-fold and CD34+ cells 330-fold, regardless of the starting CD34 number. Even though the unmanipulated unit was chosen for its greater desirability, SR-1 cultured units led to significantly more CD34+ cells and reconstituted blood cells more rapidly after six months in patients in which the treated unit predominated over the unmanipulated unit.

Some caution is still required. It will take further study to determine whether these expanded cells are effective as a stand-alone graft, rather than simply in combination with unmanipulated units. The answer will have a huge impact on the number of necessary umbilical cords. Additionally, the safety study only involved 17 patients, all with hematological malignancy. Larger and wider studies of both the safety and efficacy of SR-1 expansion units are certainly needed. Toxicity in children, for example, has yet to be evaluated. But initial results show Wagner et al. may have significantly reduced the need to dig for stem cell gold, allowing us to turn a few coins into an enormous treasure.

J. E. Wagner Jr. et al., Phase I/II trial of StemRegenin-1 expanded umbilical cord blood hematopoietic stem cells supports testing as a stand-alone graft. Cell Stem Cell 18, 144–155 (2016). [Abstract]

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