Understanding mechanisms yields novel approaches to reduce radiotherapy-related xerostomia

Luijk, Peter van; Langendijk, Johannes A.; Coppes, Robert P.

doi:10.21037/atm.2017.02.02

Cited by 3 publications

(2 citation statements)

References 7 publications

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“…As frequently noted by authors of studies reporting regional or voxel-wise analyses, strong correlations between doses in different regions or even organs complicate the interpretation of the results. However, the combination with independent development and testing of the hypothesis in preclinical models provides confidence in the interpretations described above [119].…”

Section: Parotid Gland Major Ductsmentioning

confidence: 89%

Regional Responses in Radiation-Induced Normal Tissue Damage

Voshart

Wiedemann

Luijk

et al. 2021

Cancers

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Normal tissue side effects remain a major concern in radiotherapy. The improved precision of radiation dose delivery of recent technological developments in radiotherapy has the potential to reduce the radiation dose to organ regions that contribute the most to the development of side effects. This review discusses the contribution of regional variation in radiation responses in several organs. In the brain, various regions were found to contribute to radiation-induced neurocognitive dysfunction. In the parotid gland, the region containing the major ducts was found to be critical in hyposalivation. The heart and lung were each found to exhibit regional responses while also mutually affecting each other’s response to radiation. Sub-structures critical for the development of side effects were identified in the pancreas and bladder. The presence of these regional responses is based on a non-uniform distribution of target cells or sub-structures critical for organ function. These characteristics are common to most organs in the body and we therefore hypothesize that regional responses in radiation-induced normal tissue damage may be a shared occurrence. Further investigations will offer new opportunities to reduce normal tissue side effects of radiotherapy using modern and high-precision technologies.

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Section: Parotid Gland Major Ductsmentioning

confidence: 89%

Regional Responses in Radiation-Induced Normal Tissue Damage

Voshart

Wiedemann

Luijk

et al. 2021

Cancers

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“…Nonetheless, the longstanding problem in this area is how to achieve growth (i.e., proliferation of differentiated tissue) without that growth becoming uncontrolled (i.e., development of tumorigenic cells), and studies are ongoing in an attempt to achieve such a balance with each of the scaffolds listed above. Additional efforts have involved the use stem cells, 27–29 which appear to promote glandular regeneration; however, this therapy alone is insufficient to adequately treat hyposalivation for two reasons. First, it is difficult to transplant stem cell suspensions into a targeted area, as they disperse throughout the tissue once injected, which in turn can lead to dilution of cell suspension into the blood stream and a related decrease in regenerative effects.…”

Section: Introductionmentioning

confidence: 99%

Using cell sheets to regenerate mouse submandibular glands

et al. 2019

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Temperature-responsive polymer grafted tissue culture dishes release cells as confluent living sheets in response to small changes in temperature, with recovered cell sheets retaining cell–cell communications, functional extracellular matrices and tissue-like behaviors. These features promote tissue regeneration and improve transplantation efficacy in various tissues including cartilage, heart, kidney, liver, endometrium, cornea, middle ear, periodontium, and esophageal living sheet transplants. However, the functional effects of cell sheets for salivary gland regeneration to treat hyposalivation have not yet been studied. Thus, the present study aims to both establish the viability of thermoresponsive cell sheets for use in salivary glands and then explore the delivery option (i.e., single vs. multiple layers) that would result in the most complete tissue growth in terms of cell differentiation and recovered tissue integrity. Results indicate that single cell sheets form polarized structures that maintain cell–cell junctions and secretory granules in vitro while layering of two-single cell sheets forms a glandular-like pattern in vitro. Moreover, double layer cell sheets enhance tissue formation, cell differentiation and saliva secretion in vivo. In contrast, single cell sheets demonstrated only modest gains relative to the robust growth seen with the double layer variety. Together, these data verify the utility of thermoresponsive cell sheets for use in salivary glands and indicates the double layer form to provide the best option in terms of cell differentiation and recovered tissue integrity, thereby offering a potential new therapeutic strategy for treating hyposalivation.

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