Hematopoietic stem cell regeneration enhanced by ectopic expression of ROS-detoxifying enzymes in transplant mice.
Open accessAbstract
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.
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Ectopic expression of manganese superoxide dismutase and catalase in HSCs reduces IR-induced HSC injury.
“ectopic expression of manganese superoxide dismutase and catalase in HSCs reduces IR-induced HSC injury.39”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [39]
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- Authors
- Miao, W., XuFeng, R., Park, M.-R., Gu, H., Hu, L., Kang, J. W., Ma, S., Liang, P. H., Li, Y., Cheng, H., Yu, H., Epperly, M., Greenberger, J., & Cheng, T.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- University of Pittsburgh (US)
- Corresponding author
- Cheng, Tao
- ORCID
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 21
- Issue
- 2
- Pages
- 423-432
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC3594016
- OpenAlex
- W2089961057
- Cited by
- 37
- References
- 44
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 4 · 2017: 5 · 2016: 2 · 2015: 5 · 2014: 5 · 2013: 1 · 2012: 1
- FWCI
- 3.11
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (R01-AI080424)
- Leukemia and Lymphoma Society (1027-08, 30825017, U19AI68021)
- National Natural Science Foundation of China (81090410, 90913018)
- Ministry of Science and Technology of the People's Republic of China (2010DFB30270, 2011CB964801, 2011ZX09102-010)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- hematopoietic stem cells, reactive oxygen species, manganese superoxide dismutase, catalase, reactive oxygen species scavenging, long-term engraftment, hematopoietic progenitor cells, gamma irradiation, radiation protection, retroviral gene transfer
- MeSH terms
- Animals, Catalase, Female, Flow Cytometry, Gene Expression Regulation, Genetic Vectors, Hematopoietic Stem Cells, Humans, Mice, Inbred C57BL, Oxidation-Reduction, Retroviridae, Stem Cells, Superoxide Dismutase, Transduction, Genetic, Blotting, Western, Reactive Oxygen Species, Hematopoietic Stem Cell Transplantation, Mice
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