Radiation-induced bystander effects impair transplanted human hematopoietic stem cells via oxidative DNA damage

Hu, Linping; Yin, Xiuxiu; Zhang, Yawen; Pang, Aiming; Xie, Xiaowei; Yang, Shangda; Zhu, Caiying; Li, Yapu; Zhang, Biao; Huang, Yaojin; Tian, Yunhong; Wang, Mei; Cao, Wenbin; Chen, Shulian; Zheng, Yawei; Ma, Shihui; Fang, Dong; Hao, Sha; Feng, Sizhou; Ru, Yongxin; Cheng, Hui; Jiang, Erlie; Cheng, Tao

doi:10.1182/blood.2020007362

Cited by 33 publications

(15 citation statements)

References 52 publications

(55 reference statements)

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“…We observed bystander effects on oxidative stress responses (or oxidation-reduction processes) with their 21 involved proteins (Table 2). Bystander activation of these responses has been observed in other model systems, recently in HepG2 and normal liver cells [36], human hematopoietic progenitor and stem cells [37] and mice exosomes [38].…”

Section: Implication Of Stress Granules Il12 Pathway and Oxidative St...mentioning

confidence: 72%

Label-Free Direct Mass Spectrometry Analysis of the Bystander Effects Induced in Chondrocytes by Chondrosarcoma Cells Irradiated with X-rays and Carbon Ions

Gilbert¹,

Payet²,

Bernay³

et al. 2022

Front. Biosci. (Landmark Ed)

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Background: Radiation-induced bystander effects are induced changes in cells that were not themselves directly irradiated but were in the vicinity of a radiation path. Such effects, which occur in the microenvironment of an irradiated tumor, remain poorly understood and depend on the cell type and irradiation quality. This study aimed to evaluate bystander effects in non-irradiated chondrocytes that received conditioned medium from irradiated chondrosarcoma cells. Methods: SW1353 chondrosarcoma cells were irradiated with X-rays and carbon ions, each at 0.1 Gy and 2 Gy, and the conditioned media of the irradiated cells were transferred to T/C-28A2 chondrocytes and Human Umbilical Venous Endothelial Cells (HUVECs). The whole proteome of bystander chondrocytes was analyzed by label-free mass spectrometry, and a comparative study was performed by dose and irradiation quality. HUVECs were evaluated for inflammatory cytokine secretion. Results: The bystander response of chondrocytes to X-ray irradiation primarily affected the protein translation pathway (

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Section: Implication Of Stress Granules Il12 Pathway and Oxidative St...mentioning

confidence: 72%

Label-Free Direct Mass Spectrometry Analysis of the Bystander Effects Induced in Chondrocytes by Chondrosarcoma Cells Irradiated with X-rays and Carbon Ions

Gilbert¹,

Payet²,

Bernay³

et al. 2022

Front. Biosci. (Landmark Ed)

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“…More importantly, Cheng et al. ( 36 , 37 ) found that in transplanted human HSCs, radiation-induced bystander effects increased ROS levels, contributing to HSC damage and a decrease in transplantation efficiency. It has been hypothesized that forkhead homeobox type O transcription factors are key mediators of ROS regulation in HSCs, contributing to stem cell maintenance and the DNA damage repair response ( 38 ).…”

Section: The Seedmentioning

confidence: 99%

Recent Advancements in Poor Graft Function Following Hematopoietic Stem Cell Transplantation

Man

Yao

et al. 2022

Front. Immunol.

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Poor graft function (PGF) is a life-threatening complication that occurs after transplantation and has a poor prognosis. With the rapid development of haploidentical hematopoietic stem cell transplantation, the pathogenesis of PGF has become an important issue. Studies of the pathogenesis of PGF have resulted in some success in CD34+-selected stem cell boosting. Mesenchymal stem cells, N-acetyl-l-cysteine, and eltrombopag have also been investigated as therapeutic strategies for PGF. However, predicting and preventing PGF remains challenging. Here, we propose that the seed, soil, and insect theories of aplastic anemia also apply to PGF; CD34+ cells are compared to seeds; the bone marrow microenvironment to soil; and virus infection, iron overload, and donor-specific anti-human leukocyte antigen antibodies to insects. From this perspective, we summarize the available information on the common risk factors of PGF, focusing on its potential mechanism. In addition, the safety and efficacy of new strategies for treating PGF are discussed to provide a foundation for preventing and treating this complex clinical problem.

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“…To prevent xenogenic donor-cell rejection and to allow for their settlement in the bone marrow niche, immune deficient animals are used to prevent graft rejection, and recipient mice need to be conditioned using irradiation or chemical treatment before transplantation similar to syn-and congenic transplantation models. However, as described above, such conditioning is toxic for sinusoidal blood vessels and MSCs in the murine stem cell niche (Yin et al, 2020) and, importantly, it impairs the function of xenogenic donor HSCs promoting their senescence and apoptosis by increasing ROS levels and mitochondrial damage (Hu et al, 2021).…”

Section: Xenograft Models: Human Hsc Engraftment In the Murine Bm Nichementioning

confidence: 99%

The Hematopoietic Bone Marrow Niche Ecosystem

Fröbel

Landspersky

Perçin

et al. 2021

Front. Cell Dev. Biol.

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The bone marrow (BM) microenvironment, also called the BM niche, is essential for the maintenance of fully functional blood cell formation (hematopoiesis) throughout life. Under physiologic conditions the niche protects hematopoietic stem cells (HSCs) from sustained or overstimulation. Acute or chronic stress deregulates hematopoiesis and some of these alterations occur indirectly via the niche. Effects on niche cells include skewing of its cellular composition, specific localization and molecular signals that differentially regulate the function of HSCs and their progeny. Importantly, while acute insults display only transient effects, repeated or chronic insults lead to sustained alterations of the niche, resulting in HSC deregulation. We here describe how changes in BM niche composition (ecosystem) and structure (remodeling) modulate activation of HSCs in situ. Current knowledge has revealed that upon chronic stimulation, BM remodeling is more extensive and otherwise quiescent HSCs may be lost due to diminished cellular maintenance processes, such as autophagy, ER stress response, and DNA repair. Features of aging in the BM ecology may be the consequence of intermittent stress responses, ultimately resulting in the degeneration of the supportive stem cell microenvironment. Both chronic stress and aging impair the functionality of HSCs and increase the overall susceptibility to development of diseases, including malignant transformation. To understand functional degeneration, an important prerequisite is to define distinguishing features of unperturbed niche homeostasis in different settings. A unique setting in this respect is xenotransplantation, in which human cells depend on niche factors produced by other species, some of which we will review. These insights should help to assess deviations from the steady state to actively protect and improve recovery of the niche ecosystem in situ to optimally sustain healthy hematopoiesis in experimental and clinical settings.

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Radiation-induced bystander effects impair transplanted human hematopoietic stem cells via oxidative DNA damage

Cited by 33 publications

References 52 publications

Label-Free Direct Mass Spectrometry Analysis of the Bystander Effects Induced in Chondrocytes by Chondrosarcoma Cells Irradiated with X-rays and Carbon Ions

Label-Free Direct Mass Spectrometry Analysis of the Bystander Effects Induced in Chondrocytes by Chondrosarcoma Cells Irradiated with X-rays and Carbon Ions

Recent Advancements in Poor Graft Function Following Hematopoietic Stem Cell Transplantation

The Hematopoietic Bone Marrow Niche Ecosystem

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