scholarly journals Diverse progenitor cells preserve salivary gland ductal architecture after radiation-induced damage

Development ◽  
2018 ◽  
Vol 145 (21) ◽  
pp. dev166363 ◽  
Author(s):  
Alison J. May ◽  
Noel Cruz-Pacheco ◽  
Elaine Emmerson ◽  
Eliza A. Gaylord ◽  
Kerstin Seidel ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Progenitor Cells ◽  
Radiation Induced

scholarly journals Diverse progenitor cells preserve salivary gland ductal architecture after radiation induced damage

2018 ◽  
Author(s):  
Alison J. May ◽  
Noel Cruz-Pacheco ◽  
Elaine Emmerson ◽  
Kerstin Seidel ◽  
Sara Nathan ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Progenitor Cells ◽  
Tissue Architecture ◽  
Cellular Mechanisms ◽  
Ductal Cells ◽  
Differentiated Cells ◽  
Organ Systems ◽  
Radiation Induced ◽  
Summary Statement ◽  
Do So

AbstractThe ductal system of the salivary gland has long been postulated to be resistant to radiation-induced damage, a common outcome incurred by head and neck cancer patients receiving radiotherapy. Yet, whether the ducts are capable of regenerating after genotoxic injury, or if damage to ductal cells induces lineage plasticity, as has been reported in other organ systems, remains unknown. Here, we show that two ductal progenitor populations marked by KRT14 and KIT exclusively maintain non-overlapping ductal compartments after radiation exposure but do so through distinct cellular mechanisms. KRT14+ progenitor cells are fast cycling cells that proliferate in response to radiation-induced damage in a sustained manner and divide asymmetrically to produce differentiated cells of the larger granulated ducts. Conversely, KIT+ cells are long lived progenitors for the intercalated ducts that undergo few cell divisions either during homeostasis or after gamma radiation, thus maintaining ductal architecture in the near absence of cell turnover. Together, these data illustrate the regenerative capacity of the salivary ducts and highlight the heterogeneity in the damage responses used by salivary progenitor cells to maintain tissue architecture.Summary StatementThe salivary gland ductal network is maintained during homeostasis and after genotoxic injury by diverse progenitors that respond differentially to radiation induced damage.

scholarly journals The Radiation-Induced Regenerative Response of Adult Tissue-Specific Stem Cells: Models and Signaling Pathways

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 855
Author(s):  
Paola Serrano Martinez ◽  
Lorena Giuranno ◽  
Marc Vooijs ◽  
Robert P. Coppes
Keyword(s):  
Signaling Pathways ◽  
Progenitor Cells ◽  
Tissue Regeneration ◽  
Normal Tissue ◽  
Cellular Response ◽  
Adult Tissue ◽  
Tissue Specific ◽  
Radiation Induced

Radiotherapy is involved in the treatment of many cancers, but damage induced to the surrounding normal tissue is often inevitable. Evidence suggests that the maintenance of homeostasis and regeneration of the normal tissue is driven by specific adult tissue stem/progenitor cells. These tasks involve the input from several signaling pathways. Irradiation also targets these stem/progenitor cells, triggering a cellular response aimed at achieving tissue regeneration. Here we discuss the currently used in vitro and in vivo models and the involved specific tissue stem/progenitor cell signaling pathways to study the response to irradiation. The combination of the use of complex in vitro models that offer high in vivo resemblance and lineage tracing models, which address organ complexity constitute potential tools for the study of the stem/progenitor cellular response post-irradiation. The Notch, Wnt, Hippo, Hedgehog, and autophagy signaling pathways have been found as crucial for driving stem/progenitor radiation-induced tissue regeneration. We review how these signaling pathways drive the response of solid tissue-specific stem/progenitor cells to radiotherapy and the used models to address this.

scholarly journals The evolving definition of salivary gland stem cells

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Cecilia Rocchi ◽  
Lara Barazzuol ◽  
Rob P. Coppes
Keyword(s):  
Stem Cells ◽  
Salivary Gland ◽  
Adult Stem Cell ◽  
Cell Types ◽  
Research Field ◽  
New Therapeutic Approaches ◽  
Recent Developments ◽  
Radiation Induced ◽  
Definition Of

AbstractDysfunction of the salivary gland and irreversible hyposalivation are the main side effects of radiotherapy treatment for head and neck cancer leading to a drastic decrease of the quality of life of the patients. Approaches aimed at regenerating damaged salivary glands have been proposed as means to provide long-term restoration of tissue function in the affected patients. In studies to elucidate salivary gland regenerative mechanisms, more and more evidence suggests that salivary gland stem/progenitor cell behavior, like many other adult tissues, does not follow that of the hard-wired professional stem cells of the hematopoietic system. In this review, we provide evidence showing that several cell types within the salivary gland epithelium can serve as stem/progenitor-like cells. While these cell populations seem to function mostly as lineage-restricted progenitors during homeostasis, we indicate that upon damage specific plasticity mechanisms might be activated to take part in regeneration of the tissue. In light of these insights, we provide an overview of how recent developments in the adult stem cell research field are changing our thinking of the definition of salivary gland stem cells and their potential plasticity upon damage. These new perspectives may have important implications on the development of new therapeutic approaches to rescue radiation-induced hyposalivation.

scholarly journals Mechanism of Action of Diallyl Sulphide in Ameliorating the Hematopoietic Radiation Injury

2021 ◽  
Author(s):  
Omika Katoch ◽  
Mrinalini Tiwari ◽  
Namita Kalra ◽  
Paban K. Agrawala
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Progenitor Cells ◽  
Hematopoietic Stem ◽  
Proliferation And Differentiation ◽  
Stem And Progenitor Cells ◽  
Radiation Induced ◽  
Medicinal Properties ◽  
Marrow Cellularity

AbstractDiallyl sulphide (DAS), the pungent component of garlic, is known to have several medicinal properties and has recently been shown to have radiomitigative properties. The present study was performed to better understand its mode of action in rendering radiomitigation. Evaluation of the colonogenic ability of hematopoietic progenitor cells (HPCs) on methocult media, proliferation and differentiation of hematopoietic stem cells (HSCs), and transplantation of stem cells were performed. The supporting tissue of HSCs was also evaluated by examining the histology of bone marrow and in vitro colony-forming unit–fibroblast (CFU-F) count. Alterations in the levels of IL-5, IL-6 and COX-2 were studied as a function of radiation or DAS treatment. It was observed that an increase in proliferation and differentiation of hematopoietic stem and progenitor cells occurred by postirradiation DAS administration. It also resulted in increased circulating and bone marrow homing of transplanted stem cells. Enhancement in bone marrow cellularity, CFU-F count, and cytokine IL-5 level were also evident. All those actions of DAS that could possibly add to its radiomitigative potential and can be attributed to its HDAC inhibitory properties, as was observed by the reversal radiation induced increase in histone acetylation.

Metaphase-Based Cytogenetic Approach Identifies Radiation-Induced Chromosome and Chromatid Aberrations in Zebrafish Embryos

2021 ◽  
Author(s):  
Halida Thanveer Asana Marican ◽  
Hongyuan Shen
Keyword(s):  
Animal Model ◽  
Radiation Exposure ◽  
Progenitor Cells ◽  
Chromosome Aberrations ◽  
Structural Changes ◽  
Current Knowledge ◽  
Living Organism ◽  
Zebrafish Embryos ◽  
Radiation Induced

Metaphase-based cytogenetic methods based on scoring of chromosome aberrations for the estimation of the radiation dose received provide a powerful approach for evaluating the associated risk upon radiation exposure and form the bulk of our current knowledge of radiation-induced chromosome damages. They mainly rely on inducing quiescent peripheral lymphocytes into proliferation and blocking them at metaphases to quantify the damages at the chromosome level. However, human organs and tissues demonstrate various sensitivity towards radiation and within them, self-proliferating progenitor/stem cells are believed to be the most sensitive populations. The radiation-induced chromosome aberrations in these cells remain largely unknown, especially in the context of an intact living organism. Zebrafish is an ideal animal model for research into this aspect due to their small size and the large quantities of progenitor cells present during the embryonic stages. In this study, we employ a novel metaphase-based cytogenetic approach on zebrafish embryos and demonstrate that chromosome-type and chromatid-type aberrations could be identified in progenitor cells at different cell-cycle stages at the point of radiation exposure. Our work positions zebrafish at the forefront as a useful animal model for studying radiation-induced chromosome structural changes in vivo.

scholarly journals Catalase Inhibits Ionizing Radiation-Induced Apoptosis in Hematopoietic Stem and Progenitor Cells

2015 ◽  
Vol 24 (11) ◽  
pp. 1342-1351 ◽  
Author(s):  
Xia Xiao ◽  
Hongmei Luo ◽  
Kenneth N. Vanek ◽  
Amanda C. LaRue ◽  
Bradley A. Schulte ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Progenitor Cells ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells ◽  
Radiation Induced ◽  
Induced Apoptosis

scholarly journals Cellular senescence contributes to radiation-induced hyposalivation by affecting the stem/progenitor cell niche

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Xiaohong Peng ◽  
Yi Wu ◽  
Uilke Brouwer ◽  
Thijmen van Vliet ◽  
Boshi Wang ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Cellular Senescence ◽  
Progenitor Cell ◽  
Tissue Degeneration ◽  
Cycle Arrest ◽  
Radiation Induced ◽  
Secretory Phenotype ◽  
Cell Niche ◽  
Gland Function ◽  
Formation Efficiency

Abstract Radiotherapy for head and neck cancer is associated with impairment of salivary gland function and consequent xerostomia, which has a devastating effect on the quality of life of the patients. The mechanism of radiation-induced salivary gland damage is not completely understood. Cellular senescence is a permanent state of cell cycle arrest accompanied by a secretory phenotype which contributes to inflammation and tissue deterioration. Genotoxic stresses, including radiation-induced DNA damage, are known to induce a senescence response. Here, we show that radiation induces cellular senescence preferentially in the salivary gland stem/progenitor cell niche of mouse models and patients. Similarly, salivary gland-derived organoids show increased expression of senescence markers and pro-inflammatory senescence-associated secretory phenotype (SASP) factors after radiation exposure. Clearance of senescent cells by selective removal of p16Ink4a-positive cells by the drug ganciclovir or the senolytic drug ABT263 lead to increased stem cell self-renewal capacity as measured by organoid formation efficiency. Additionally, pharmacological treatment with ABT263 in mice irradiated to the salivary glands mitigates tissue degeneration, thus preserving salivation. Our data suggest that senescence in the salivary gland stem/progenitor cell niche contributes to radiation-induced hyposalivation. Pharmacological targeting of senescent cells may represent a therapeutic strategy to prevent radiotherapy-induced xerostomia.

Prevention of radiation induced xerostomia by surgical transfer of submandibular salivary gland into the submental space

2003 ◽  
Vol 66 (3) ◽  
pp. 283-289 ◽  
Author(s):  
Naresh Jha ◽  
Hadi Seikaly ◽  
Jeff Harris ◽  
David Williams ◽  
Richard Liu ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Submandibular Salivary Gland ◽  
Radiation Induced
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