Acute graft-versus-host disease(a GVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation(allo-HSCT). However,the mechanisms of a GVHD are not well understood. We aim to investigate the roles of the three angiogenic factors: angiopoietin-1(Ang-1),Ang-2 and vascular endothelial growth factor(VEGF) in the development of a GVHD. Twenty-one patients who underwent allo-HSCT were included in our study. The dynamic changes of Ang-1,Ang-2 and VEGF were monitored in patients before and after allo-HSCT. In vitro,endothelial cells(ECs) were treated with TNF-α in the presence or absence of Ang-1,and then the Ang-2 level in the cell culture medium and the tubule formation by ECs were evaluated. After allo-HSCT,Ang-1,Ang-2 and VEGF all exhibited significant variation,suggesting these factors might be involved in the endothelial damage in transplantation. Patients with a GVHD had lower Ang-1 level at day 7 but higher Ang-2 level at day 21 than those without a GVHD,implying that Ang-1 may play a protective role in early phase yet Ang-2 is a promotion factor to a GVHD. In vitro,TNF-α promoted the release of Ang-2 by ECs and impaired tubule formation of ECs,which were both weakened by Ang-1,suggesting that Ang-1 may play a protective role in a GVHD by influencing the secretion of Ang-2,consistent with our in vivo tests. It is concluded that monitoring changes of these factors following allo-HSCT might help to identify patients at a high risk for a GVHD.
Although mesenchymal stem cells(MSCs) are increasingly used to treat graft-versus-host disease(GVHD), their immune regulatory mechanism in the process is elusive. The present study aimed to investigate the curative effect of third-party umbilical cord blood-derived human MSCs(UCB-h MSCs) on GVHD patients after allogeneic hematopoietic stem cell transplantation(allo-HSCT) and their immune regulatory mechanism. Twenty-four refractory GVHD patients after allo-HSCT were treated with UCB-h MSCs. Immune cells including T lymphocyte subsets, NK cells, Treg cells and dendritic cells(DCs) and cytokines including interleukin-17(IL-17) and tumor necrosis factor-alpha(TNF-α) were monitored before and after MSCs transfusion. The results showed that the symptoms of GVHD were alleviated significantly without increased relapse of primary disease and transplant-related complications after MSCs transfusion. The number of CD3+, CD3+CD4+ and CD3+CD8+ cells decreased significantly, and that of NK cells remained unchanged, whereas the number of CD4+ and CD8+ Tregs increased and reached a peak at 4 weeks; the number of mature DCs, and the levels of TNF-α and IL-17 decreased and reached a trough at 2 weeks. It was concluded that MSCs ameliorate GVHD and spare GVL effect via immunoregulations.
