Hematopoietic Stem and Progenitor Cell Migration After Hypofractionated Radiation Therapy in a Murine Model

Kane, Jonathan L.; Krueger, S.A.; Dilworth, J.T.; Torma, J.; Wilson, George D.; Marples, Brian; Madlambayan, Gerard J.

doi:10.1016/j.ijrobp.2013.08.044

Cited by 7 publications

(7 citation statements)

References 17 publications

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“…To further validate the involvement of immune enhancement in LDR‐induced tumor inhibition, HDR pretreatment was carried out before LDR treatment to impair the immune function as an inverse validation. The dose of HDR was 1 Gy, which was considered insufficient to directly inhibit tumor growth because the effective dose of radiation to treat Lewis lung cancer in mice is 13 Gy or more . As expected, we found that HDR markedly impaired immune function, resulting in decreased splenocyte proliferation and cytokine production.…”

Section: Discussionsupporting

confidence: 77%

Validating the pivotal role of the immune system in low‐dose radiation‐induced tumor inhibition in Lewis lung cancer‐bearing mice

Zhou

Zhang

et al. 2018

Cancer Medicine

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Although low‐dose radiation (LDR) possesses the two distinct functions of inducing hormesis and adaptive responses, which result in immune enhancement and tumor inhibition, its clinical applications have not yet been elucidated. The major obstacle that hinders the application of LDR in the clinical setting is that the mechanisms underlying induction of tumor inhibition are unclear, and the risks associated with LDR are still unknown. Thus, to overcome this obstacle and elucidate the mechanisms mediating the antitumor effects of LDR, in this study, we established an in vivo lung cancer model to investigate the participation of the immune system in LDR‐induced tumor inhibition and validated the pivotal role of the immune system by impairing immunity with high‐dose radiation (HDR) of 1 Gy. Additionally, the LDR‐induced adaptive response of the immune system was also observed by sequential HDR treatment in this mouse model. We found that LDR‐activated T cells and natural killer cells and increased the cytotoxicity of splenocytes and the infiltration of T cells in the tumor tissues. In contrast, when immune function was impaired by HDR pretreatment, LDR could not induce tumor inhibition. However, when LDR was administered before HDR, the immunity could be protected from impairment, and tumor growth could be inhibited to some extent, indicating the induction of the immune adaptive response by LDR. Therefore, we demonstrated that immune enhancement played a key role in LDR‐induced tumor inhibition. These findings emphasized the importance of the immune response in tumor radiotherapy and may help promote the application of LDR as a novel approach in clinical practice.

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Section: Discussionsupporting

confidence: 77%

Validating the pivotal role of the immune system in low‐dose radiation‐induced tumor inhibition in Lewis lung cancer‐bearing mice

Zhou

Zhang

et al. 2018

Cancer Medicine

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“…It has been reported that prior irradiation leads to increased recruitment of cells to the BM (34, 35), however, we observed that initial BM homing was independent of prior BM ablation (Fig. 3).…”

Section: Discussionmentioning

confidence: 46%

Bone Marrow Cell Trafficking Analyzed by 89Zr-oxine Positron Emission Tomography in a Murine Transplantation Model

Asiedu

Koyasu

Szajek

et al. 2017

Clinical Cancer Research

102

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Purpose The success of hematopoietic stem cell transplantation (HSCT) depends on donor cell homing to the bone marrow (BM). However, there is no reliable method of noninvasively monitoring the kinetics and distribution of transferred cells. Using Zirconium-89 (89Zr)-oxine cell labeling combined with positron emission tomography (PET) imaging, we sought to visualize and quantify donor cell homing in a mouse BM transplantation model. Experimental Design The effect of 89Zr-oxine labeling on BM cell viability and differentiation was evaluated in vitro. 89Zr-labeled BM cells (2×107 cells, 16.6 kBq/106 cells) were transferred intravenously and serial microPET images were obtained (n=5). The effect of a CXCR4 inhibitor, plerixafor, (5 mg/kg) and granulocyte-colony stimulation factor (G-CSF, 2.5 μg) on BM homing and mobilization were examined (n=4). Engraftment of the transferred 89Zr-labeled cells was evaluated (n=3). Results 89Zr-oxine-labeled BM cells showed delayed proliferation, but differentiated normally. Transferred BM cells rapidly migrated to the BM, spleen, and liver (n=5). Approximately 36% of donor cells homed to the BM within 4 h, irrespective of prior BM ablation. Inhibition of CXCR4 by plerixafor alone or with G-CSF significantly blocked the BM homing (p<0.0001, vs non-treated, at 2 h), confirming a crucial role of the CXCR4-CXCL12 system. Mobilization of approximately 0.64% of pre-transplanted BM cells induced a 3.8-fold increase of circulating BM cells. 89Zr-labeled donor cells engrafted as well as non-labeled cells. Conclusions 89Zr-oxine PET imaging reveals rapid BM homing of transferred BM cells without impairment of their stem cell functions, and thus, could provide useful information for optimizing HSCT.

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“…Umbilical cord blood is considered as an alternative source for stem cell transplantation and therapy due to its hematopoietic and mesenchymal properties 20 . For both HSCs and leukemia stem cells (LSCs), specific gene expression programs distinguish them from their differentiated progenies 21 . Human HSCs are a primary target of radiation-induced leukemogenesis and provide a correlation cellular model for evaluating the risk of cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Therapeutic delivery of miR142-3p in ATRT cells suggested effective reduction in its lethality by repressing tumor growth, inhibiting invasion, enhancing radiosensitivity, and prolonging survival time in orthotropic-transplanted immunocompromised mice 29 . Moreover miR-142-3p directly targets CD133 to regulate its ability to confer cancer and stem cell-like features in HCC 21 .…”

Section: Discussionmentioning

confidence: 99%

MiRNA-142-3p increases radiosensitivity in human umbilical cord blood mononuclear cells by inhibiting the expression of CD133

Fang

Liu

Lei

et al. 2018

Sci Rep

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This study is to explore the molecular regulation mechanism of CD133 which is associated with malignancy and poor prognosis of blood system diseases. CD133+HUCB-MNC (human umbilical cord blood mononuclear cells) and CD133−HUCB-MNC were isolated and amplificated from umbilical cord blood, and then were exposed to different doses of radiation and subjected to a clonogenic assay. CCK-8 kit was used to detect cell viability, Annexin V-FITC/PI cell apoptosis detection kit was used for the detection of apoptotic cells and the BrdU assay was performed by flow cytometry. The expression of protein was analyzed by western blots. The profile of miRNA expression in response to radiation was examined and validated by RT-PCR. miR-142-3p inhibited the expression of CD133 in umbilical cord blood mononuclear cells to increase radiosensitivity. CD133+HUCB-MNC cells were more radioresistant compared with CD133−HUCB-MNC cells. CD133+HUCB-MNC cells showed higher p-AKT and p-ERK levels after radiation. And miR-142-3p acted on 3′UTR of CD133 mRNA to inhibit CD133 expression. Moreover, miRNA-142-3p mimic increased radiosensitivity in CD133+HUCB-MNC cells. Our results elucidated a novel regulation pathway in hematopoietic stem cells and suggested a potential therapeutic approach for blood system diseases therapy.

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Hematopoietic Stem and Progenitor Cell Migration After Hypofractionated Radiation Therapy in a Murine Model

Cited by 7 publications

References 17 publications

Validating the pivotal role of the immune system in low‐dose radiation‐induced tumor inhibition in Lewis lung cancer‐bearing mice

Validating the pivotal role of the immune system in low‐dose radiation‐induced tumor inhibition in Lewis lung cancer‐bearing mice

Bone Marrow Cell Trafficking Analyzed by 89Zr-oxine Positron Emission Tomography in a Murine Transplantation Model

MiRNA-142-3p increases radiosensitivity in human umbilical cord blood mononuclear cells by inhibiting the expression of CD133

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