Morphologic and histochemical studies on the differing radiosensitivity of ductular and acinar cells of the rat submandibular gland

Abok, Kisia; Brunk, Ulf T.; Jung, B.; Ericsson, Jan L. E.

doi:10.1007/bf02889885

Cited by 118 publications

(83 citation statements)

References 46 publications

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“…36 The salivary gland has long been known to exhibit a paradoxically acute sensitivity to radiation therapy. 47,82,83 The loss of terminally differentiated secretory cells after radiation has been suggested to occur through radical-mediated damage of secretory granules 84 or the plasma membrane. 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.…”

Section: Resultsmentioning

confidence: 99%

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: 99%

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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“…Some hypotheses have been raised in an effort to explain this acute radiation-induced damage. This radiosensitivity could be explained by the presence of granules in serous cells, rich in transition metals such as zinc, iron and manganese, which are released into cytoplasm, causing autolysis and cell death (13). On the other hand, Peter et al (14) stimulated the degranulation of acinar cells, causing release of these metals prior to irradiation and observed that cell recovery was attributable rather to the action of isoproterenol than to the removal of metal ions from the acinar cells.…”

Section: Discussionmentioning

confidence: 99%

Radioprotective Effect of Vitamin E in Parotid Glands: a Morphometric Analysis in Rats

et al. 2013

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The aim of this study was to evaluate the radioprotective effect of vitamin E on rat parotid glands by morphometric analysis. Sixty male rats were divided into 5 groups (n=6): control, in which animals received olive oil solution; olive oil/irradiated, in which animals received olive oil and were irradiated with a dose of 15 Gy of gamma radiation; irradiated, in which animals were irradiated with a dose of 15 Gy gamma radiation; vitamin E, which received α-tocopherol acetate solution; vitamin E/irradiated, which received α-tocopherol acetate solution before irradiation with a dose of 15 Gy gamma rays. Half of the animals were euthanized at 8 h, and the remaining at 30 days after irradiation. Both parotid glands were surgically removed and morphometric analysis of acinar cells was performed. Data were subjected to two-way ANOVA and Tukey's test (α=0.05). Morphometric analysis showed a significant reduction in the number of parotid acinar cells at 30 days in olive oil/irradiated and irradiated groups. In groups evaluated over time a significant reduction was shown at 30 days in olive oil/irradiated and irradiated groups, indicating that ionizing radiation caused tissue damage. The vitamin E/irradiated group presented more acinar cells than the irradiated group, but no statistically significant difference was observed (p>0.05). In conclusion, vitamin E seems to have failed as a radioprotective agent on acinar cells in rat parotid glands. R a d i o p r o t e c t i v e E f f e c t o f V i t a m i n E i n Pa r o t i d G l a n d s :

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“…In the parotid, the surviving acinar cells then proliferate and restore the acini within two weeks (Leeb, 1978 (Cherry and Glucksmann, 1959;Sholley et al, 1974;Sodicoff et al, 1974;Abok et al, 1984). Regeneration of acini can occur after the minor damage caused by mild to moderate (e.g., from 600 to 1600 rad) doses, but after heavy (greater than 6000 rad) irradiation, the acini of the parotid gland all but disappear.…”

Section: Activities During Developmentmentioning

confidence: 99%

Salivary Glands: A Paradigm for Diversity of Gland Development

Denny

Ball

Redman

1997

Critical Reviews in Oral Biology & Medicine

177

171

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The major salivary glands of mammals are represented by three pairs of organs that cooperate functionally to produce saliva for the oral cavity. While each type of gland produces a signature secretion that complements the secretions from the other glands, there is also redundancy as evidenced by secretion of functionally similar and, in some cases, identical products in the three glands. This, along with their common late initiation of development, in fetal terms, their similarities in developmental pattern, and their proximate sites of origin, suggests that a common regulatory cascade may have been shared until shortly before the onset of overt gland development. Furthermore, occasional ectopic differentiation of individual mature secretory cells in the wrong" gland suggests that control mechanisms responsible for the distinctive cellular composition of each gland also share many common steps, with only minor differences providing the impetus for diversification. To begin to address this area, we examine here the origins of the salivary glands by reviewing the expression patterns of several genes with known morphogenetic potential that may be involved based on developmental timing and location. The possibility that factors leading to determination of the sites of mammalian salivary gland development might be homologous to the regulatory cascade leading to salivarv gland formation in Drosophila is also evaluated. In a subsequent section, cellular phenotypes of neonatal and adult glands are compared and evaluated for insights into the mechanisms and lineages leading to cellular diversification. Finally, the phenomena of proliferation, repair, and regeneration in adult salivary glands are reviewed, with emphasis on the extent to which the cellular diversity is reversible and which cell type other than stem cells has the ability to redifferentiate into other cell types.

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Morphologic and histochemical studies on the differing radiosensitivity of ductular and acinar cells of the rat submandibular gland

Cited by 118 publications

References 46 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

Radioprotective Effect of Vitamin E in Parotid Glands: a Morphometric Analysis in Rats

Salivary Glands: A Paradigm for Diversity of Gland Development

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