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Cells
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Stem Cells and Irradiation
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Stem Cells and Irradiation

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Stem Cells".

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 49357

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Dr. Alain Chapel

E-Mail Website1 Website2
Guest Editor
1. IRSN PSE Sante SERAMED, Radiobiology of Medical Exposure Laboratory (LRMed), 92262 Fontenay, France
2. UPMC Univ Paris 06, UMR_S938 CDR Saint-Antoine, Stem Cell Proliferation and Differentiation, F-75012 Paris, France
Interests: regeneratiive medecine; radiobiologie; stem cells; clinical trials; cancer; health; skin; blood; bowel; tumor; bladder

Special Issue Information

Dear Colleagues,

The main difficulty of radiotherapy is to destroy cancer cells without depletion of healthy tissue. Stem cells and cancers are tightly interrelated. On one hand, radiosensitivity/radioressistance of cancer stem cells affects the radiocurability of tumors. On the other hand, radiosensitivity is responsible for the stem cell depletion of organs at risk exposed to irradiation. Efficient solide cancer destruction is limited by the preservation of organ homeostasis. For this reason, targeted irradiation is an effective cancer therapy, but damage inflicted to normal tissues surrounding the tumor may cause severe complications. The consequences of stem cell depletion of healthy tissue irradiated are acute and chronic radiation diseases.

Research on the radiosensitivity of cancer stem cells and adult stem cells associated with tissue regeneration medicine will bring forth the solution for optimal radiocurability associated with long-term patients’ quality of life.

Dr. Alain Chapel
Guest Editor

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Keywords

  • stem cells
  • cancer
  • irradiation
  • radiotherapy
  • radiobiology
  • radiosensitivity
  • tissue
  • organ at risk
  • radiation disease
  • regenerative medicine
  • cell therapy

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Published Papers (11 papers)

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Editorial

Jump to: Research, Review

2 pages, 179 KiB  
Editorial
Stem Cells and Irradiation
by Alain Chapel
Cells 2021, 10(4), 760; https://doi.org/10.3390/cells10040760 - 30 Mar 2021
Cited by 4 | Viewed by 3327
Abstract
The main difficulty of radiotherapy is to destroy cancer cells without depletion of healthy tissue [...] Full article
(This article belongs to the Special Issue Stem Cells and Irradiation)

Research

Jump to: Editorial, Review

14 pages, 3392 KiB  
Article
Radiation-Activated PI3K/AKT Pathway Promotes the Induction of Cancer Stem-Like Cells via the Upregulation of SOX2 in Colorectal Cancer
by Ji-Hye Park, Young-Heon Kim, Sehwan Shim, Areumnuri Kim, Hyosun Jang, Su-Jae Lee, Sunhoo Park, Songwon Seo, Won Il Jang, Seung Bum Lee and Min-Jung Kim
Cells 2021, 10(1), 135; https://doi.org/10.3390/cells10010135 - 12 Jan 2021
Cited by 25 | Viewed by 3373
Abstract
The current treatment strategy for patients with aggressive colorectal cancer has been hampered by resistance to radiotherapy and chemotherapy due to the existence of cancer stem-like cells (CSCs). Recent studies have shown that SOX2 expression plays an important role in the maintenance of [...] Read more.
The current treatment strategy for patients with aggressive colorectal cancer has been hampered by resistance to radiotherapy and chemotherapy due to the existence of cancer stem-like cells (CSCs). Recent studies have shown that SOX2 expression plays an important role in the maintenance of CSC properties in colorectal cancer. In this study, we investigated the induction and regulatory role of SOX2 following the irradiation of radioresistant and radiosensitive colorectal cancer cells. We used FACS and western blotting to analyze SOX2 expression in cells. Among the markers of colorectal CSCs, the expression of CD44 increased upon irradiation in radioresistant cells. Further analysis revealed the retention of CSC properties with an upregulation of SOX2 as shown by enhanced resistance to radiation and metastatic potential in vitro. Interestingly, both the knockdown and overexpression of SOX2 led to increase in CD44+ population and induction of CSC properties in colorectal cancer following irradiation. Furthermore, selective genetic and pharmacological inhibition of the PI3K/AKT pathway, but not the MAPK pathway, attenuated SOX2-dependent CD44 expression and metastatic potential upon irradiation in vitro. Our findings suggested that SOX2 regulated by radiation-induced activation of PI3K/AKT pathway contributes to the induction of colorectal CSCs, thereby highlighting its potential as a therapeutic target. Full article
(This article belongs to the Special Issue Stem Cells and Irradiation)
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21 pages, 9123 KiB  
Article
Keap1-Nrf2 Pathway Regulates ALDH and Contributes to Radioresistance in Breast Cancer Stem Cells
by Dinisha Kamble, Megharani Mahajan, Rohini Dhat and Sandhya Sitasawad
Cells 2021, 10(1), 83; https://doi.org/10.3390/cells10010083 - 6 Jan 2021
Cited by 43 | Viewed by 5424
Abstract
Tumor recurrence after radiotherapy due to the presence of breast cancer stem cells (BCSCs) is a clinical challenge, and the mechanism remains unclear. Low levels of ROS and enhanced antioxidant defenses are shown to contribute to increasing radioresistance. However, the role of Nrf2-Keap1-Bach1 [...] Read more.
Tumor recurrence after radiotherapy due to the presence of breast cancer stem cells (BCSCs) is a clinical challenge, and the mechanism remains unclear. Low levels of ROS and enhanced antioxidant defenses are shown to contribute to increasing radioresistance. However, the role of Nrf2-Keap1-Bach1 signaling in the radioresistance of BCSCs remains elusive. Fractionated radiation increased the percentage of the ALDH-expressing subpopulation and their sphere formation ability, promoted mesenchymal-to-epithelial transition and enhanced radioresistance in BCSCs. Radiation activated Nrf2 via Keap1 silencing and enhanced the tumor-initiating capability of BCSCs. Furthermore, knockdown of Nrf2 suppressed ALDH+ population and stem cell markers, reduced radioresistance by decreasing clonogenicity and blocked the tumorigenic ability in immunocompromised mice. An underlying mechanism of Keap1 silencing could be via miR200a, as we observed a significant increase in its expression, and the promoter methylation of Keap1 or GSK-3β did not change. Our data demonstrate that ALDH+ BCSC population contributes to breast tumor radioresistance via the Nrf2-Keap1 pathway, and targeting this cell population with miR200a could be beneficial but warrants detailed studies. Our results support the notion that Nrf2-Keap1 signaling controls mesenchymal–epithelial plasticity, regulates tumor-initiating ability and promotes the radioresistance of BCSCs. Full article
(This article belongs to the Special Issue Stem Cells and Irradiation)
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11 pages, 2700 KiB  
Article
Evaluation of the Effectiveness of Mesenchymal Stem Cells of the Placenta and Their Conditioned Medium in Local Radiation Injuries
by Vitaliy Brunchukov, Tatiana Astrelina, Daria Usupzhanova, Anna Rastorgueva, Irina Kobzeva, Victoria Nikitina, Sergei Lishchuk, Elena Dubova, Konstantin Pavlov, Valentin Brumberg, Marc Benderitter and Alexander Samoylov
Cells 2020, 9(12), 2558; https://doi.org/10.3390/cells9122558 - 29 Nov 2020
Cited by 9 | Viewed by 2282
Abstract
Background: The search for an effective therapy for local radiation injuries (LRI) is urgent; one option is mesenchymal stem cells (MSC) derived from the placenta and their conditioned medium for the regenerative processes of the skin. Methods: We used 80 animals, randomly assigned [...] Read more.
Background: The search for an effective therapy for local radiation injuries (LRI) is urgent; one option is mesenchymal stem cells (MSC) derived from the placenta and their conditioned medium for the regenerative processes of the skin. Methods: We used 80 animals, randomly assigned to four groups: control (C) animals that did not receive therapy; control with the introduction of culture medium concentrate (CM); introduction of MSCs (PL); introduction of CMPL. LRI modeling was performed on an X-ray machine at a dose of 110 Gy. Histological and immunohistochemical tests were performed. Results: On the 112th day, the area of the open wound surface in the CMPL group was 6.7 times less than in the control group. Complete healing of the open wound surface of the skin in the CM group was observed in 40%, in CMPL 60%, in the PL group 20%, and in the C group there were no animals with a prolonged wound defect. A decrease in inflammatory processes was observed in the CMPL group. Conclusions: the use of a concentrate of conditioned MSCs (CMPL group) in severe LRI in laboratory animals accelerates the transition of the wound process to the stage of regeneration and epithelization. Full article
(This article belongs to the Special Issue Stem Cells and Irradiation)
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17 pages, 2885 KiB  
Article
Exposure of Human Skin Organoids to Low Genotoxic Stress Can Promote Epithelial-to-Mesenchymal Transition in Regenerating Keratinocyte Precursor Cells
by Sophie Cavallero, Renata Neves Granito, Daniel Stockholm, Peggy Azzolin, Michèle T. Martin and Nicolas O. Fortunel
Cells 2020, 9(8), 1912; https://doi.org/10.3390/cells9081912 - 18 Aug 2020
Cited by 8 | Viewed by 4569
Abstract
For the general population, medical diagnosis is a major cause of exposure to low genotoxic stress, as various imaging techniques deliver low doses of ionizing radiation. Our study investigated the consequences of low genotoxic stress on a keratinocyte precursor fraction that includes stem [...] Read more.
For the general population, medical diagnosis is a major cause of exposure to low genotoxic stress, as various imaging techniques deliver low doses of ionizing radiation. Our study investigated the consequences of low genotoxic stress on a keratinocyte precursor fraction that includes stem and progenitor cells, which are at risk for carcinoma development. Human skin organoids were bioengineered according to a clinically-relevant model, exposed to a single 50 mGy dose of γ rays, and then xeno-transplanted in nude mice to follow full epidermis generation in an in vivo context. Twenty days post-xenografting, mature skin grafts were sampled and analyzed by semi-quantitative immuno-histochemical methods. Pre-transplantation exposure to 50 mGy of immature human skin organoids did not compromise engraftment, but half of xenografts generated from irradiated precursors exhibited areas displaying focal dysplasia, originating from the basal layer of the epidermis. Characteristics of epithelial-to-mesenchymal transition (EMT) were documented in these dysplastic areas, including loss of basal cell polarity and cohesiveness, epithelial marker decreases, ectopic expression of the mesenchymal marker α-SMA and expression of the EMT promoter ZEB1. Taken together, these data show that a very low level of radiative stress in regenerating keratinocyte stem and precursor cells can induce a micro-environment that may constitute a favorable context for long-term carcinogenesis. Full article
(This article belongs to the Special Issue Stem Cells and Irradiation)
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Review

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18 pages, 345 KiB  
Review
Therapeutic Potential of Mesenchymal Stromal Cells and Extracellular Vesicles in the Treatment of Radiation Lesions—A Review
by Mohi Rezvani
Cells 2021, 10(2), 427; https://doi.org/10.3390/cells10020427 - 18 Feb 2021
Cited by 12 | Viewed by 3268
Abstract
Ionising radiation-induced normal tissue damage is a major concern in clinic and public health. It is the most limiting factor in radiotherapy treatment of malignant diseases. It can also cause a serious harm to populations exposed to accidental radiation exposure or nuclear warfare. [...] Read more.
Ionising radiation-induced normal tissue damage is a major concern in clinic and public health. It is the most limiting factor in radiotherapy treatment of malignant diseases. It can also cause a serious harm to populations exposed to accidental radiation exposure or nuclear warfare. With regard to the clinical use of radiation, there has been a number of modalities used in the field of radiotherapy. These includes physical modalities such modified collimators or fractionation schedules in radiotherapy. In addition, there are a number of pharmacological agents such as essential fatty acids, vasoactive drugs, enzyme inhibitors, antioxidants, and growth factors for the prevention or treatment of radiation lesions in general. However, at present, there is no standard procedure for the treatment of radiation-induced normal tissue lesions. Stem cells and their role in tissue regeneration have been known to biologists, in particular to radiobiologists, for many years. It was only recently that the potential of stem cells was studied in the treatment of radiation lesions. Stem cells, immediately after their successful isolation from a variety of animal and human tissues, demonstrated their likely application in the treatment of various diseases. This paper describes the types and origin of stem cells, their characteristics, current research, and reviews their potential in the treatment and regeneration of radiation induced normal tissue lesions. Adult stem cells, among those mesenchymal stem cells (MSCs), are the most extensively studied of stem cells. This review focuses on the effects of MSCs in the treatment of radiation lesions. Full article
(This article belongs to the Special Issue Stem Cells and Irradiation)
16 pages, 366 KiB  
Review
Mesenchymal Stem Cells for Mitigating Radiotherapy Side Effects
by Kai-Xuan Wang, Wen-Wen Cui, Xu Yang, Ai-Bin Tao, Ting Lan, Tao-Sheng Li and Lan Luo
Cells 2021, 10(2), 294; https://doi.org/10.3390/cells10020294 - 1 Feb 2021
Cited by 25 | Viewed by 4160
Abstract
Radiation therapy for cancers also damages healthy cells and causes side effects. Depending on the dosage and exposure region, radiotherapy may induce severe and irreversible injuries to various tissues or organs, especially the skin, intestine, brain, lung, liver, and heart. Therefore, promising treatment [...] Read more.
Radiation therapy for cancers also damages healthy cells and causes side effects. Depending on the dosage and exposure region, radiotherapy may induce severe and irreversible injuries to various tissues or organs, especially the skin, intestine, brain, lung, liver, and heart. Therefore, promising treatment strategies to mitigate radiation injury is in pressing need. Recently, stem cell-based therapy generates great attention in clinical care. Among these, mesenchymal stem cells are extensively applied because it is easy to access and capable of mesodermal differentiation, immunomodulation, and paracrine secretion. Here, we summarize the current attempts and discuss the future perspectives about mesenchymal stem cells (MSCs) for mitigating radiotherapy side effects. Full article
(This article belongs to the Special Issue Stem Cells and Irradiation)
20 pages, 1550 KiB  
Review
Mesenchymal Stem Cell-Derived Exosomes: Biological Function and Their Therapeutic Potential in Radiation Damage
by Xiaoyu Pu, Siyang Ma, Yan Gao, Tiankai Xu, Pengyu Chang and Lihua Dong
Cells 2021, 10(1), 42; https://doi.org/10.3390/cells10010042 - 30 Dec 2020
Cited by 25 | Viewed by 4824
Abstract
Radiation-induced damage is a common occurrence in cancer patients who undergo radiotherapy. In this setting, radiation-induced damage can be refractory because the regeneration responses of injured tissues or organs are not well stimulated. Mesenchymal stem cells have become ideal candidates for managing radiation-induced [...] Read more.
Radiation-induced damage is a common occurrence in cancer patients who undergo radiotherapy. In this setting, radiation-induced damage can be refractory because the regeneration responses of injured tissues or organs are not well stimulated. Mesenchymal stem cells have become ideal candidates for managing radiation-induced damage. Moreover, accumulating evidence suggests that exosomes derived from mesenchymal stem cells have a similar effect on repairing tissue damage mainly because these exosomes carry various bioactive substances, such as miRNAs, proteins and lipids, which can affect immunomodulation, angiogenesis, and cell survival and proliferation. Although the mechanisms by which mesenchymal stem cell-derived exosomes repair radiation damage have not been fully elucidated, we intend to translate their biological features into a radiation damage model and aim to provide new insight into the management of radiation damage. Full article
(This article belongs to the Special Issue Stem Cells and Irradiation)
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20 pages, 870 KiB  
Review
Chronic Inflammation and Radiation-Induced Cystitis: Molecular Background and Therapeutic Perspectives
by Carole Helissey, Sophie Cavallero, Clément Brossard, Marie Dusaud, Cyrus Chargari and Sabine François
Cells 2021, 10(1), 21; https://doi.org/10.3390/cells10010021 - 24 Dec 2020
Cited by 33 | Viewed by 7867
Abstract
Radiation cystitis is a potential complication following the therapeutic irradiation of pelvic cancers. Its clinical management remains unclear, and few preclinical data are available on its underlying pathophysiology. The therapeutic strategy is difficult to establish because few prospective and randomized trials are available. [...] Read more.
Radiation cystitis is a potential complication following the therapeutic irradiation of pelvic cancers. Its clinical management remains unclear, and few preclinical data are available on its underlying pathophysiology. The therapeutic strategy is difficult to establish because few prospective and randomized trials are available. In this review, we report on the clinical presentation and pathophysiology of radiation cystitis. Then we discuss potential therapeutic approaches, with a focus on the immunopathological processes underlying the onset of radiation cystitis, including the fibrotic process. Potential therapeutic avenues for therapeutic modulation will be highlighted, with a focus on the interaction between mesenchymal stromal cells and macrophages for the prevention and treatment of radiation cystitis. Full article
(This article belongs to the Special Issue Stem Cells and Irradiation)
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20 pages, 1145 KiB  
Review
Current and Future Perspectives of the Use of Organoids in Radiobiology
by Peter W. Nagle and Robert P. Coppes
Cells 2020, 9(12), 2649; https://doi.org/10.3390/cells9122649 - 9 Dec 2020
Cited by 24 | Viewed by 4905
Abstract
The majority of cancer patients will be treated with radiotherapy, either alone or together with chemotherapy and/or surgery. Optimising the balance between tumour control and the probability of normal tissue side effects is the primary goal of radiation treatment. Therefore, it is imperative [...] Read more.
The majority of cancer patients will be treated with radiotherapy, either alone or together with chemotherapy and/or surgery. Optimising the balance between tumour control and the probability of normal tissue side effects is the primary goal of radiation treatment. Therefore, it is imperative to understand the effects that irradiation will have on both normal and cancer tissue. The more classical lab models of immortal cell lines and in vivo animal models have been fundamental to radiobiological studies to date. However, each of these comes with their own limitations and new complementary models are required to fill the gaps left by these traditional models. In this review, we discuss how organoids, three-dimensional tissue-resembling structures derived from tissue-resident, embryonic or induced pluripotent stem cells, overcome the limitations of these models and thus have a growing importance in the field of radiation biology research. The roles of organoids in understanding radiation-induced tissue responses and in moving towards precision medicine are examined. Finally, the limitations of organoids in radiobiology and the steps being made to overcome these limitations are considered. Full article
(This article belongs to the Special Issue Stem Cells and Irradiation)
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14 pages, 841 KiB  
Review
Rationale for the Use of Radiation-Activated Mesenchymal Stromal/Stem Cells in Acute Respiratory Distress Syndrome
by Isabel Tovar, Rosa Guerrero, Jesús J. López-Peñalver, José Expósito and José Mariano Ruiz de Almodóvar
Cells 2020, 9(9), 2015; https://doi.org/10.3390/cells9092015 - 2 Sep 2020
Cited by 14 | Viewed by 4007
Abstract
We have previously shown that the combination of radiotherapy with human umbilical-cord-derived mesenchymal stromal/stem cells (MSCs) cell therapy significantly reduces the size of the xenotumors in mice, both in the directly irradiated tumor and in the distant nonirradiated tumor or its metastasis. We [...] Read more.
We have previously shown that the combination of radiotherapy with human umbilical-cord-derived mesenchymal stromal/stem cells (MSCs) cell therapy significantly reduces the size of the xenotumors in mice, both in the directly irradiated tumor and in the distant nonirradiated tumor or its metastasis. We have also shown that exosomes secreted from MSCs preirradiated with 2 Gy are quantitatively, functionally and qualitatively different from the exosomes secreted from nonirradiated mesenchymal cells, and also that proteins, exosomes and microvesicles secreted by MSCs suffer a significant change when the cells are activated or nonactivated, with the amount of protein present in the exosomes of the preirradiated cells being 1.5 times greater compared to those from nonirradiated cells. This finding correlates with a dramatic increase in the antitumor activity of the radiotherapy when is combined with MSCs or with preirradiated mesenchymal stromal/stem cells (MSCs*). After the proteomic analysis of the load of the exosomes released from both irradiated and nonirradiated cells, we conclude that annexin A1 is the most important and significant difference between the exosomes released by the cells in either status. Knowing the role of annexin A1 in the control of hypoxia and inflammation that is characteristic of acute respiratory-distress syndrome (ARDS), we designed a hypothetical therapeutic strategy, based on the transplantation of mesenchymal stromal/stem cells stimulated with radiation, to alleviate the symptoms of patients who, due to pneumonia caused by SARS-CoV-2, require to be admitted to an intensive care unit for patients with life-threatening conditions. With this hypothesis, we seek to improve the patients’ respiratory capacity and increase the expectations of their cure. Full article
(This article belongs to the Special Issue Stem Cells and Irradiation)
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