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Research Highlight | May 15, 2018

Blocking donor T cell–mediated TNF? signaling can enhance positive effects of stem cell transplantation

Drs. Zandstra & Weijia3
Photo: Study author Dr. Weijia Wang

A collaboration between Swiss and Canadian research institutes has shown an effective way to enhance human hematopoietic stem and progenitor cell engraftment after stem cell transplantation by blocking donor T cell-mediated TNFα signalling.

The study, published in Science Translational Medicine (December 2017), was led by Dr. Peter Zandstra (University of Toronto) and Dr. Weijia Wang (formerly at the University of Toronto and now in collaborator Timm Schroeder’s lab at ETH Zürich) with collaboration from renowned TFRI-funded cancer researcher Dr. John Dick (Princess Margaret Cancer Centre). Results suggested that tumour necrosis factor-alpha (TNFα), which is produced by some of the differentiated cells after stem cell transplantation, is harmful for the survival of blood stem cells. Further, by using one of the clinically available drugs that block TNFα, higher numbers of blood stem cells and more diverse types of blood cells were found in the bone marrow after two weeks of transplant in a preclinical mouse model.    

 Allogeneic hematopoietic stem cell transplantation (HSCT) is a form of therapy for patients living with hematologic diseases including leukemia, and is potentially curative – yet up to 70 per cent of patients do not have a matched related donor. One cell source of stem cell transplantations is umbilical cord blood, but the number of stem cells available in individual umbilical cord blood units is often limiting. This can lead to delayed hematopoietic recovery and a higher risk of graft failure, both major complications that can lead to patient death post-transplant.

The findings in the present study have the potential to dramatically improve patient outcomes after a transplant, and provide a strong basis for conducting clinical trials to see whether the use of TNFα blockers (which are used to treat auto-immune diseases like arthritis and psoriasis) could improve the outcomes of people who receive blood stem cell transplants. For example, if this strategy boosts the survival rate of blood stem cells in humans, smaller grafts could be used. This would vastly increase the pool of usable umbilical cord blood donations, making stem cell transplants more feasible – not only for blood cancers, but also for auto-immune diseases, like Crohn’s disease or even HIV.

Study: Enhanced human hematopoietic stem and progenitor cell engraftment by blocking donor T cell-mediated TNFα signalling

Authors: Weijia Wang, Hisaki Fujii, Hye Jin Kim, Karin Hermans, Tatiana Usenko, Stephanie Xie, Zhi-Juan Luo, Jennifer Ma, Cristina Lo Celso, John E. Dick, Timm Schroeder, Joerg Krueger, Donna Wall, R. Maarten Egeler, Peter W. Zandstra.

 Funding: This study was partially funded by a grant from the Terry Fox Research Institute.

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