Blockade of TNFα to Improve Human CD34+ Cell Repopulating Activity in Allogeneic Stem Cell Transplantation.

摘要: Early release of TNFα after hematopoietic stem cell transplantation (HSCT) correlates with development acute graft-vs.-host disease (GVHD). Here we tested the effect and alloreactive T cells on early HSC genotype function. Addition (10 ng/ml) in liquid cultures CD34+ for 6-72 h resulted downregulation genes associated activity, such as DNMT3A, DNMT3B, TET1, TET2, SOX2, NANOG, OCT4, whereas no significant was observed DNMT1 GATA2 expression. These findings were reversed by using an anti-TNFα antibody. Similar gene when co-cultured 48-72 h, this partially prevented rapamycin pre-incubated 48 transplanted irradiated NOD-SCID ɤnull (NSG) mice showed a reduced myeloid engraftment compared to control mice. By xenograft model recently developed our lab, co-transplanted allogeneic lymphocytes at 1:0.1 ratio one group that also received etanercept (TNFα inhibitor) 100 μg intra-peritoneum (i.p.) days -1,+1,+3,+5 post-HSCT, group. At 6 weeks post-transplant, had significantly higher number marrow huCD45+CD34+CD38- (p = 0.03) huCD45+CD3+ splenic 0.04) controls. The repopulating activity from treated vs. controls secondary transplants. Although overall similar two groups, isolated recipients greater expression cell-associated CD45+CD34+CD38- than 0.03). Our suggest increase post-transplant can affect long-term engraftment, blockade transplant may limit cytokine-mediated suppressive