On the mechanism of salivary gland radiosensitivity

Konings, Antonius W.T.; Coppes, Robert P.; Vissink, Arjan

doi:10.1016/j.ijrobp.2004.12.051

Cited by 292 publications

(254 citation statements)

References 53 publications

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“…44 A process common to both of these phenomena is the formation of hydroxyl radicals from the irradiation of water, which subsequently abstracts hydrogens from unsaturated fatty acids in the plasma membrane and generates peroxyl radicals that propagate through adjacent fatty acids molecules, resulting in membrane destabilization. 46 We believe that primary SMG cells are exhibiting a similar sensitivity to ROS here and hypothesize that ROS generated by methacrylate-based chain addition polymerizations damage the SMG cell membrane lipids, leading to increased intracellular oxidative stress and cell death.…”

Section: Resultsmentioning

confidence: 57%

“…31,42,43 In this work, methods have been explored to encapsulate, culture, and characterize primary SMG cells within PEG hydrogels, with the long-term goal of developing a tissue engineering approach for the salivary gland. Due to the sensitivity of salivary gland cells to reactive oxygen species (ROS), [44][45][46][47][48] we examined the effects of two forms of radical-mediated hydrogel polymerization: chain addition methacrylate-based polymerizations and step-growth thiol-ene polymerizations on primary SMG cells. PEG hydrogels are bioinert, 26 and they lack cell-matrix and cell-cell interactions that are commonly utilized to maintain survivability of sensitive cell types.…”

mentioning

confidence: 99%

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Development of Poly(Ethylene Glycol) Hydrogels for Salivary Gland Tissue Engineering Applications

Shubin

Felong

Graunke

et al. 2015

Tissue Engineering Part A

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More than 40,000 patients are diagnosed with head and neck cancers annually in the United States with the vast majority receiving radiation therapy. Salivary glands are irreparably damaged by radiation therapy resulting in xerostomia, which severely affects patient quality of life. Cell-based therapies have shown some promise in mouse models of radiation-induced xerostomia, but they suffer from insufficient and inconsistent gland regeneration and accompanying secretory function. To aid in the development of regenerative therapies, poly(ethylene glycol) hydrogels were investigated for the encapsulation of primary submandibular gland (SMG) cells for tissue engineering applications. Different methods of hydrogel formation and cell preparation were examined to identify cytocompatible encapsulation conditions for SMG cells. Cell viability was much higher after thiol-ene polymerizations compared with conventional methacrylate polymerizations due to reduced membrane peroxidation and intracellular reactive oxygen species formation. In addition, the formation of multicellular microspheres before encapsulation maximized cell-cell contacts and increased viability of SMG cells over 14-day culture periods. Thiol-ene hydrogel-encapsulated microspheres also promoted SMG proliferation. Lineage tracing was employed to determine the cellular composition of hydrogel-encapsulated microspheres using markers for acinar (Mist1) and duct (Keratin5) cells. Our findings indicate that both acinar and duct cell phenotypes are present throughout the 14 day culture period. However, the acinar:duct cell ratios are reduced over time, likely due to duct cell proliferation. Altogether, permissive encapsulation methods for primary SMG cells have been identified that promote cell viability, proliferation, and maintenance of differentiated salivary gland cell phenotypes, which allows for translation of this approach for salivary gland tissue engineering applications.

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Section: Resultsmentioning

confidence: 57%

mentioning

confidence: 99%

Development of Poly(Ethylene Glycol) Hydrogels for Salivary Gland Tissue Engineering Applications

Shubin

Felong

Graunke

et al. 2015

Tissue Engineering Part A

View full text Add to dashboard Cite

show abstract

“…5 Hyposalivation exacerbates dental caries and periodontal disease and causes problems of mastication, swallowing, sleep, and speech, a burning sensation of the mouth, and dysgeusia, which severely impair the quality of life of patients. The irreversible hyposalivation is caused by the loss or impairment of saliva-producing acinar cells and their replacement by connective tissue and fibrosis, which has been attributed to the loss of functional glandular stem/progenitor cells 6 and the impairment of parasympathetic innervation 7 and microvessels. 8 Current treatments for IR-induced xerostomia, such as artificial saliva and saliva secretion stimulators, can only temporarily relieve these symptoms.…”

Section: Introductionmentioning

confidence: 99%

Rescue Effects and Underlying Mechanisms of IntraglandShhGene Delivery on Irradiation-Induced Hyposalivation

et al. 2016

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“…For radiotherapeutic treatment of head and neck tumors, the salivary glands are one of the tissues at risk. Exposure of the salivary gland to radiation often results in a progressive loss of gland function within the first weeks of radiotherapy (1). The reduction in saliva flow rate and alteration of salivary composition may persist during the rest of the patient's life, leading to complications, including oral dryness, nocturnal oral discomfort, increased risk for oral infections, dental caries, and difficulties in speech, which severely hamper the quality of life (2,3).…”

mentioning

confidence: 99%

Mobilization of Bone Marrow Stem Cells by Granulocyte Colony-Stimulating Factor Ameliorates Radiation-Induced Damage to Salivary Glands

Lombaert¹,

Wierenga²,

Kok³

et al. 2006

Clinical Cancer Research

141

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Purpose: One of the major reasons for failure of radiotherapeutic cancer treatment is the limitation in dose that can be applied to the tumor because of coirradiation of the normal healthy tissue. Late radiation-induced damage reduces the quality of life of the patient and may even be life threatening. Replacement of the radiation-sterilized stem cells with unirradiated autologous stem cells may restore the tissue function. Here, we assessed the potential of granulocyte colony-stimulating factor (G-CSF)–mobilized bone marrow–derived cells (BMC) to regenerate and functionally restore irradiated salivary glands used as a model for normal tissue damage. Experimental Design: Male-eGFP+ bone marrow chimeric female C57BL/6 mice were treated with G-CSF, 10 to 60 days after local salivary gland irradiation. Four months after irradiation, salivary gland morphology and flow rate were assessed. Results: G-CSF treatment induced homing of large number of labeled BMCs to the submandibular glands after irradiation. These animals showed significant increased gland weight, number of acinar cells, and salivary flow rates. Donor cells expressed surface markers specific for hematopoietic or endothelial/mesenchymal cells. However, salivary gland acinar cells neither express the G-CSF receptor nor contained the GFP/Y chromosome donor cell label. Conclusions: The results show that BMCs home to damaged salivary glands after mobilization and induce repair processes, which improve function and morphology. This process does not involve transdifferentiation of BMCs to salivary gland cells. Mobilization of BMCs could become a promising modality to ameliorate radiation-induced complications after radiotherapy.

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On the mechanism of salivary gland radiosensitivity

Cited by 292 publications

References 53 publications

Development of Poly(Ethylene Glycol) Hydrogels for Salivary Gland Tissue Engineering Applications

Development of Poly(Ethylene Glycol) Hydrogels for Salivary Gland Tissue Engineering Applications

Rescue Effects and Underlying Mechanisms of IntraglandShhGene Delivery on Irradiation-Induced Hyposalivation

Mobilization of Bone Marrow Stem Cells by Granulocyte Colony-Stimulating Factor Ameliorates Radiation-Induced Damage to Salivary Glands

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