title: Hematopoietic stem cell regeneration enhanced by ectopic expression of ROS-detoxifying enzymes in transplant mice.
abstract: High levels of reactive oxygen species (ROS) can exhaust hematopoietic stem cells (HSCs). Thus, maintaining a low state of redox in HSCs by modulating ROS-detoxifying enzymes may augment the regeneration potential of HSCs. Our results show that basal expression of manganese superoxide dismutase (MnSOD) and catalase were at low levels in long-term and short-term repopulating HSCs, and administration of a MnSOD plasmid and lipofectin complex (MnSOD-PL) conferred radiation protection on irradiated recipient mice. To assess the intrinsic role of elevated MnSOD or catalase in HSCs and hematopoietic progenitor cells, the MnSOD or catalase gene was overexpressed in mouse hematopoietic cells via retroviral transduction. The impact of MnSOD and catalase on hematopoietic progenitor cells was mild, as measured by colony-forming units (CFUs). However, overexpressed catalase had a significant beneficial effect on long-term engraftment of transplanted HSCs, and this effect was further enhanced after an insult of low-dose γ-irradiation in the transplant mice. In contrast, overexpressed MnSOD exhibited an insignificant effect on long-term engraftment of transplanted HSCs, but had a significant beneficial effect after an insult of sublethal irradiation. Taken together, these results demonstrate that HSC function can be enhanced by ectopic expression of ROS-detoxifying enzymes, especially after radiation exposure in vivo.
authors.affiliation: State Key Laboratory for Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Miao
authors.forename: Richard
authors.initials: R
authors.lastname: Xufeng
authors.forename: Moo-Rim
authors.initials: MR
authors.lastname: Park
authors.forename: Haihui
authors.initials: H
authors.lastname: Gu
authors.forename: Linping
authors.initials: L
authors.lastname: Hu
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Kang
authors.forename: Shihui
authors.initials: S
authors.lastname: Ma
authors.forename: Paulina H
authors.initials: PH
authors.lastname: Liang
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Li
authors.forename: Haizi
authors.initials: H
authors.lastname: Cheng
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.forename: Michael
authors.initials: M
authors.lastname: Epperly
authors.forename: Joel
authors.initials: J
authors.lastname: Greenberger
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics; D013234:Stem Cells; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D014161:Transduction, Genetic
chemical_list: D017382:Reactive Oxygen Species; D002374:Catalase; D013482:Superoxide Dismutase