An Inflammatory Environment: Donor Granulocytes Mediate Endothelial Regeneration Following Transplantation

The kinetics of hematopoietic reconstitution following stem cell transplantation is a clinically import parameter. While extensive research has focused on cell autonomous factors that can impact on reconstitution capacity of donor hematopoietic stem cells (HSCs), comparatively little work has focused on regeneration of the bone marrow niche components that are also damaged following treatment with myeloablative conditioning agents. In a recent article in Nature Medicine, the group of Daniel Lucas used the mouse transplantation model to explore the degree to which the bone marrow endothelial niche regenerates after total body irradiation, and whether this impacts upon hematopoietic reconstitution. Surprisingly, they found that donor bone marrow granulocytes were able to improve the recovery of endothelial cells following irradiation, resulting in enhanced hematopoietic engraftment (Fig. 1). On a mechanistic level, the authors discovered that the key signaling molecule mediating this effect was granulocyte-derived tumor necrosis factor-α (TNF-α), which has previously been ascribed both positive and negative effects on HSCs. Not only does this article uncover a completely new indirect mechanism via which TNF-α may impact on HSC biology, but it also highlights a potential novel approach to improve bone marrow transplantation by focusing on enhancing the recovery of the HSC niche.

Figure 1.

Immunofluorescence image showing the association between transferred granulocytes (white, Ly6G) with regenerating sinusoids (red, CD31/CD144) and arterioles (red and green, CD31/CD144⁺Nestin-GFP^bright) in Nestin-gfp recipients 6 days after lethal irradiation and transplantation. Scale bar = 50 μm. Image provided by Daniel Lucas, University of Michigan School of Medicine.

Link to article: https://www.nature.com/articles/nm.4448.