title: An acute negative bystander effect of γ-irradiated recipients on transplanted hematopoietic stem cells.
abstract: Ultimate success of hematopoietic stem cell transplantation (HSCT) depends not only on donor HSCs themselves but also on the host environment. Total body irradiation is a component in various host conditioning regimens for HSCT. It is known that ionizing radiation exerts "bystander effects" on nontargeted cells and that HSCs transplanted into irradiated recipients undergo proliferative exhaustion. However, whether irradiated recipients pose a proliferation-independent bystander effect on transplanted HSCs is unclear. In this study, we found that irradiated mouse recipients significantly impaired the long-term repopulating ability of transplanted mouse HSCs shortly (∼ 17 hours) after exposure to irradiated hosts and before the cells began to divide. There was an increase of acute cell death associated with accelerated proliferation of the bystander hematopoietic cells. This effect was marked by dramatic down-regulation of c-Kit, apparently because of elevated reactive oxygen species. Administration of an antioxidant chemical, N-acetylcysteine, or ectopically overexpressing a reactive oxygen species scavenging enzyme, catalase, improved the function of transplanted HSCs in irradiated hosts. Together, this study provides evidence for an acute negative, yet proliferation-independent, bystander effect of irradiated recipients on transplanted HSCs, thereby having implications for HSCT in both experimental and clinical scenarios in which total body irradiation is involved.
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Shen
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.forename: Paulina H
authors.initials: PH
authors.lastname: Liang
authors.forename: Haizi
authors.initials: H
authors.lastname: Cheng
authors.forename: Richard
authors.initials: R
authors.lastname: XuFeng
authors.forename: Youzhong
authors.initials: Y
authors.lastname: Yuan
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Clayton A
authors.initials: CA
authors.lastname: Smith
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
mesh_terms: D000208:Acute Disease; D000818:Animals; D024201:Bystander Effect / Q000276:immunology / Q000528:radiation effects*; D002478:Cells, Cultured; D057809:HEK293 Cells; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000502:physiology / Q000528:radiation effects*; D006801:Humans; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D011833:Radiation Injuries, Experimental / Q000209:etiology* / Q000276:immunology; D019172:Transplantation Conditioning / Q000009:adverse effects; D014916:Whole-Body Irradiation / Q000009:adverse effects