Adipose-derived mesenchymal stem cells regenerate radioiodine-induced salivary gland damage in a murine model

Kim, Ji Won; Kim, Jeong Mi; Choi, Mi Eun; Kim, Seok-Ki; Kim, Young-Mo; Choi, Jeong‐Seok

doi:10.1038/s41598-019-51775-9

Cited by 30 publications

(36 citation statements)

References 30 publications

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“…AQP5 has been used as a salivary acinar cell marker and displayed elevated gene expression in SGs of NOD mice treated with either spleen or mesenchymal stem cells [ 175 , 176 ]. Elevated gene expression of AQP1, AQP4 and AQP5 have been measured in mice models of xerostomia treated with a cell extract from either bone marrow or mesenchymal stem cells, which reduced salivary focus score, and restored saliva and tear flow rates [ 177 , 178 , 179 ].…”

Section: Therapeutic Strategies Aiming At Aqps To Treat Xerostomiamentioning

confidence: 99%

“…Elevated AQP5 expression was noted after rescuing damaged SGs using adipose-derived mesenchymal stem cells following radioiodine therapy, which is usually used for patients with thyroid cancer [ 179 ]. Using an irradiation-injured SG mouse model, elevated AQP5 expression levels were consistently observed following treatment with a bone marrow cell extract in a mouse model in which SGs were injured by either a single- or fractionated-dose of irradiation [ 180 , 181 , 182 ].…”

Section: Therapeutic Strategies Aiming At Aqps To Treat Xerostomiamentioning

confidence: 99%

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Insight into Salivary Gland Aquaporins

D’Agostino

Elkashty

Chivasso

et al. 2020

Cells

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The main role of salivary glands (SG) is the production and secretion of saliva, in which aquaporins (AQPs) play a key role by ensuring water flow. The AQPs are transmembrane channel proteins permeable to water to allow water transport across cell membranes according to osmotic gradient. This review gives an insight into SG AQPs. Indeed, it gives a summary of the expression and localization of AQPs in adult human, rat and mouse SG, as well as of their physiological role in SG function. Furthermore, the review provides a comprehensive view of the involvement of AQPs in pathological conditions affecting SG, including Sjögren’s syndrome, diabetes, agedness, head and neck cancer radiotherapy and SG cancer. These conditions are characterized by salivary hypofunction resulting in xerostomia. A specific focus is given on current and future therapeutic strategies aiming at AQPs to treat xerostomia. A deeper understanding of the AQPs involvement in molecular mechanisms of saliva secretion and diseases offered new avenues for therapeutic approaches, including drugs, gene therapy and tissue engineering. As such, AQP5 represents a potential therapeutic target in different strategies for the treatment of xerostomia.

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Section: Therapeutic Strategies Aiming At Aqps To Treat Xerostomiamentioning

confidence: 99%

Section: Therapeutic Strategies Aiming At Aqps To Treat Xerostomiamentioning

confidence: 99%

Insight into Salivary Gland Aquaporins

D’Agostino

Elkashty

Chivasso

et al. 2020

Cells

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“…The available treatments for SG atrophy are temporary and limited to systemic parasympathomimetic drugs such as pilocarpine, sialogogues, and artificial saliva substitutes and SG is not regenerate functionally ( See et al., 2019 ). New therapeutic options have shifted to regenerating SG cells by stem cell transplantation ( Lombaert et al., 2017 ; Kim et al., 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…We have confirmed the nature of isolated stem cells using flow cytometery for CD105 and CD90 marker that are highly expressed in the MSCs. Cell-based therapy has been recently increasing attention for regeneration medicine such as damaged SGs ( Lombaert et al., 2017 ; Kim et al., 2019 ). MSCs are alternative source of multipotent stem cells that have been widely used to differentiation of many types of cell lineages ( Rashtbar et al., 2018 ; Shirian et al., 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Reconstruction of necrotic submandibular salivary gland using mesenchymal stem cells

Najafi

Hassan

Faraji

et al. 2020

Heliyon

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Background The efficacy of mesnchymal stem cells (MSCs) to treat the necrotic tissue of salivary glands (SGs) has yet investigated. Objective This study was conducted to investigate the potential capacity of MSCs to restore the function and regenerate the necrotic submandiular gland in the rat animal model. Methods Twenty-one Sprague–Dawley rats were provided from a breeding colony and randomly divided into three groups including the positive control or induced SG atrophy without treatment, the treatment group or induced SG atrophy with MSCs isolated transplantation and the negative control group consists of healthy rats. The atrophic and necrotic submandiular gland was induced using intraoral duct ligation of the main duct of submandiular gland for one month. The isolated stem cells were confirmed using flow cytometry for CD90 and CD 105. The isolated MSCs were cultured and injected to submandiular gland and the potential efficacy of MSCs to treat the atrophic submandibular glands was evaluated using histopathology on two weeks post-transplantation. To detect the acinar cell protein secretory granules, Alcian Blue and periodic acid shift (PAS) staining were done. For the demonstration of mitotic index or proliferation rate of the SG epithelia tissue, Ki-67 and Smbg proteins expression were evaluated using immunohistochemistry. Results The locally injected MSCs could regenerate the overall histological structure of the necrotic submandibular gland tissue within 2 weeks of post-transplantation. Alcian Blue and PAS staining indicated that the mean amount of serous and mucin secretions in the treatment group was significantly increased compared to the positive control groups. We have also found that the treatment group significantly express higher Ki-67 protein, as a diagnostic marker for cell mitosis and proliferation rate, and lower Smbg protein, as a diagnostic marker, for damage to the submandibular gland than that of control group. Conclusion This study demonstrates the therapeutic benefits of MSCs isolated from the SG in treating atrophic and necrotic SGs in a rat model. MSCs may be potential candidates for cell-based therapies targeting hypofunction of SG induced by a range of diseases or because of surgery and radiotherapy of head and neck cancers.

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“…Immunohistochemical staining. Immunohistochemical staining was performed according to a previously described protocol, with minor modifications 46 . Tumour model samples were processed as formalin-fixed paraffin-embedded tissue blocks, The sections were then cut into 4-µm-thick sections and dewaxed in xylene, rehydrated using an ethanol gradient in water, and rinsed with PBS.…”

Section: Semi-quantitative Rt-pcrmentioning

confidence: 99%

Characterisation of a subpopulation of CD133+ cancer stem cells from Chinese patients with oral squamous cell carcinoma

Zhang

Liu

et al. 2020

Sci Rep

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Cancer stem cells (CSCs) play a critical role in cancer development and growth. The aim of this study was to identify and isolate cScs from populations of primary oral squamous cell carcinoma (OSCC) cells, which were obtained from OSCC specimens and identified by cell morphology and immunohistochemical staining for keratin. CD133 + cells detected by flow cytometry comprised 0.41 ± 0.06% of primary OSCC cells and were isolated from primary OSCC cell populations using magnetic-activated cell sorting, revealing that 93.39% of high-purity CD133 + cells were in the G0/ G1 phase of the cell cycle. Additionally, the growth rate of CD133 + cells was higher than that of CD133 − cells, and in vivo tumourigenesis experiments showed that the tumourigenic ability of CD133 + cells was markedly stronger than that of CD133 − cells. Moreover, CD133 + cells showed increased chemotherapeutic resistance to cisplatin and higher self-renewal ability according to sphere-formation assay, as well as higher mRNA levels of stemness-associated genes, including NANOG, SOX2, ALDH1A1, and OCT4. These results indicated that OSCC cells, which share certain characteristics of CSCs, harbour CD133 + cells potentially responsible for OSCC aggressiveness, suggesting CD133 as a potential prognostic marker and therapeutic target. Head and neck cancer (HNC) is the sixth most common malignancy worldwide, with oral squamous cell carcinoma (OSCC) the most common type of HNC and accounting for >90% of all oral cancers 1,2. Smoking, drinking, and chewing areca nuts are considered risk factors for OSCC, which can affect any part of the mouth, including the lips, tongue, and throat 3. Furthermore, when patients develop OSCC, they experience maxillofacial deformity and psychological trauma in addition to common symptoms of cancer. Although there have been advances in surgical techniques and chemotherapeutic strategies for OSCC, the patient survival rate remains low 4. Cisplatin is the first-line chemotherapeutic drug currently used to treat patients with locally advanced, resectable OSCC; however, cisplatin resistance poses a major challenge for its clinical application 5 and is considered the critical cause of tumour recurrence in OSCC patients 6. Therefore, a better understanding of the mechanisms underlying OSCC recurrence is required to develop novel therapeutic strategies 7. Studies have increasingly focused on the roles of cancer stem cells (CSCs) in cancer invasion and recurrence 8. CSCs represent highly heterogeneous subpopulations with functional heterogeneity in their respective tumours and are characterised by infinite proliferation, self-renewal, chemotherapeutic resistance, and multidirectionality 9. The role of CSCs was previously demonstrated in the development and therapeutic resistance of liver cancer 10. Similar to their roles in other malignancies, CSCs also play a pivotal role in OSCC development and progression 11,12. The study of CSCs, also referred to as tumour-initiating cells 13 , has recently become among the most popular research dire...

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Adipose-derived mesenchymal stem cells regenerate radioiodine-induced salivary gland damage in a murine model

Cited by 30 publications

References 30 publications

Insight into Salivary Gland Aquaporins

Insight into Salivary Gland Aquaporins

Reconstruction of necrotic submandibular salivary gland using mesenchymal stem cells

Characterisation of a subpopulation of CD133+ cancer stem cells from Chinese patients with oral squamous cell carcinoma

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