An acute negative bystander effect of γ-irradiated recipients on transplanted hematopoietic stem cells.
Open accessAbstract
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.
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“damage to the HSC niche, such as induction of BM stromal cell senescence, and a negative bystander effect of TBI on HSCs, also play a role in IR-induced residual BM injury.32,33”
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 [33]
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Self-citation
- Authors
- Shen, H., Yu, H., Liang, P. H., Cheng, H., XuFeng, R., Yuan, Y., Zhang, P., Smith, C. A., & Cheng, T.
- Affiliations
- University of Pittsburgh (US)
- Departments of Radiation Oncology and
- UPMC Hillman Cancer Center (US)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Corresponding author
- Shen, Hongmei
- Yu, Hui
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2012-04-12
- Volume
- 119
- Issue
- 15
- Pages
- 3629-3637
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC3325047
- OpenAlex
- W2006848133
- Cited by
- 62
- References
- 52
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 4 · 2021: 10 · 2020: 3 · 2019: 5 · 2018: 3 · 2017: 3 · 2016: 5 · 2015: 5 · 2014: 5 · 2013: 5
- FWCI
- 3.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (30825017, 81090410)
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL070561, HL070561)
- National Institute of Allergy and Infectious Diseases (AI080424, R01AI080424)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Keywords
- hematopoietic stem cells, gamma irradiation, total body irradiation, host conditioning, CD117, reactive oxygen species, N-acetylcysteine, catalase, antioxidants
- MeSH terms
- Acute Disease, Animals, Cells, Cultured, Hematopoietic Stem Cells, Humans, Mice, Inbred C57BL, Models, Biological, Radiation Injuries, Experimental, Whole-Body Irradiation, Hematopoietic Stem Cell Transplantation, Transplantation Conditioning, Mice, Congenic, Bystander Effect, Mice, HEK293 Cells
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