Mouse parotid salivary gland organoids for the in vitro study of stem cell radiation response

Martinez, Paola Serrano; Cinat, Davide; Luijk, Peter van; Baanstra, Mirjam; Haan, Gerald de; Pringle, Sarah; Coppes, Robert P.

doi:10.1111/odi.13475

Cited by 30 publications

(15 citation statements)

References 48 publications

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“…While low dose hypersensitivity is not a new phenomenon [ 73 , 74 ], this was the first study to show the relevance of this phenomenon in stem/progenitor cells, with a potential clinical relevance. Furthermore, we have recently developed a protocol for the culturing of parotid salivary gland organoids and demonstrated that parotid gland stem cells display a similar radiosensitivity as those of submandibular salivary glands [ 75 ]. Importantly, as organoids are derived from stem/progenitor cell populations, they allow for the study of a more stem/progenitor specific response.…”

Section: Organoids and Regeneration Of Radiation-induced Damaged Tmentioning

confidence: 99%

Current and Future Perspectives of the Use of Organoids in Radiobiology

Nagle

Coppes

2020

Cells

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The majority of cancer patients will be treated with radiotherapy, either alone or together with chemotherapy and/or surgery. Optimising the balance between tumour control and the probability of normal tissue side effects is the primary goal of radiation treatment. Therefore, it is imperative to understand the effects that irradiation will have on both normal and cancer tissue. The more classical lab models of immortal cell lines and in vivo animal models have been fundamental to radiobiological studies to date. However, each of these comes with their own limitations and new complementary models are required to fill the gaps left by these traditional models. In this review, we discuss how organoids, three-dimensional tissue-resembling structures derived from tissue-resident, embryonic or induced pluripotent stem cells, overcome the limitations of these models and thus have a growing importance in the field of radiation biology research. The roles of organoids in understanding radiation-induced tissue responses and in moving towards precision medicine are examined. Finally, the limitations of organoids in radiobiology and the steps being made to overcome these limitations are considered.

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Section: Organoids and Regeneration Of Radiation-induced Damaged Tmentioning

confidence: 99%

Current and Future Perspectives of the Use of Organoids in Radiobiology

Nagle

Coppes

2020

Cells

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“…Moreover, taste bud organoids have been used to explore the effects of radiation on taste buds, suggesting SIRT1 inhibitors can promote Lgr5 + taste bud stem cell survival and mitigate radiation-induced oral mucositis (Guo et al 2019). SG organoids have also made progress in mimicking radiation damage in studying the mechanism of stem cell response to radiation (Serrano Martinez et al 2020).…”

Section: Potential Applications Of Oral Organoidsmentioning

confidence: 99%

Oral Organoids: Progress and Challenges

Gao

Liao

et al. 2021

J Dent Res

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Oral organoids are complex 3-dimensional structures that develop from stem cells or organ-specific progenitors through a process of self-organization and re-create architectures and functionalities similar to in vivo organs and tissues in the oral and maxillofacial region. Recently, striking advancements have been made in the construction and application of oral organoids of the tooth, salivary gland, and tongue. Dental epithelial and mesenchymal cells isolated from tooth germs or derived from pluripotent stem cells could generate tooth germ–like organoids by self-organization in a specific culture system. Tooth organoids can also be constructed based on tissue engineering principles by seeding stem cells on a scaffold with the bioregulatory functions of odontogenic differentiation. Two main approaches have been used to construct salivary gland organoids: 1) incubation of salivary gland–derived stem/progenitor cells in a 3-dimensional culture system to form the structure of the gland through mimicking regenerative processes and 2) inducing of pluripotent stem cells to generate embryonic salivary glands by replicating the development process. Taste bud organoids can be generated by embedding isolated circumvallate papilla tissue in Matrigel with a mixture of growth factors, while lingual epithelial organoids have been constructed using lingual stem cells in a suitable culture system containing specific signaling molecules. These oral organoids usually maintain the main functions and characteristic structures of the corresponding organ to a certain extent. Furthermore, using cells isolated from patients, oral organoids could replicate specific diseases such as maxillofacial tumors and tooth dysplasia. Until now, oral organoids have been applied in the study of mechanisms of tooth development, pathology and regeneration of the salivary gland, and precision therapeutics for tongue cancer. These findings strongly demonstrate that the organoid technique is a novel paradigm for the study of the development, pathology, and regeneration of oral and maxillofacial tissue.

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“…Such stem cell therapy is an attractive option for the long‐term treatment of hyposalivation related xerostomia induced by irradiation, but is in need of further study in animals and preliminary studies in human before it can evolve into a clinically applicable method. Future studies should also focus on a better understanding of the radiosensitivity of parotid and submandibular salivary gland tissue (Serrano Martinez et al., 2020).…”

Section: Figurementioning

confidence: 99%

“…Such stem cell therapy is an attractive option for the long-term treatment of hyposalivation related xerostomia induced by irradiation, but is in need of further study in animals and preliminary studies in human before it can evolve into a clinically applicable method. Future studies should also focus on a better understanding of the radiosensitivity of parotid and submandibular salivary gland tissue (Serrano Martinez et al, 2020).All these developments show the benefits for patients of a good cooperation between primary and secondary caregivers. The good cooperation also demonstrates what can be achieved if efforts are focused and put into practice.…”

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confidence: 97%

Cooperation as core value in an innovative era

Witjes

Vissink

2020

Oral Diseases

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Cooperation as core value in an innovative era Diagnosis, treatment, and rehabilitation of patients suffering from oral cancer are shared responsibilities of primary care givers like dentists, physicians and oral medicine specialists, and intramural secondary care specialties. Because of the complex nature of treatment and the necessity of long-term care in most patients, the treatment and follow-up of head and neck cancer patients are confined to centers with dedicated teams in most countries. Early referral of patients suspected for oral cancer is considered important because survival is related to tumor stage and primary care givers play a pivotal role in that respect (Grafton-Clarke et al., 2019). Where health care is organized with possibilities of a quick and easy referral, the risk of delayed referral is greatly reduced. dental rehabilitation after oncological surgery. Several practical issues remain to be resolved, however, such as the timing of placement of dental implants as well as the placement of dental implants in free flaps. Like for surgical planning, planning of an oral rehabilitation is supported by 3D technology. This technology supports precise placement of implants and design of prosthetic devices. Notwithstanding the long experience with dental implants, new ideas based on implant technology still emerge and become implemented in clinical practice. The application of zygoma implants after maxillectomy in combination with soft tissue flaps is an example of a creative idea finding its way into the clinic (Hackett et al., 2020). Treatment of cancer in the head and neck area is commonly accompanied by damage to the salivary glands (Barazzuol et al., 2020; Vissink et al., 2015). Damage to the salivary glands is unavoidable as the salivary glands are located superficially and the ionizing radiation has to pass salivary gland tissue to reach the tumor. While there is many approach to minimize this radiation damage to salivary gland tissue, there is yet no satisfactory therapy to treat radiation-induced salivary gland damage. A feasible option might be harvesting salivary gland tissue during, for example, a head and neck dissection procedure, isolate and proliferate stem cells from this tissue and return these stem cells to the salivary glands that are damaged by the postoperative radiotherapy. Such stem cell therapy is an attractive option for the long-term treatment of hyposalivation related xerostomia induced by irradiation, but is in need of further study in animals and preliminary studies in human before it can evolve into a clinically applicable method. Future studies should also focus on a better understanding of the radiosensitivity of parotid and submandibular salivary gland tissue (Serrano Martinez et al., 2020). All these developments show the benefits for patients of a good cooperation between primary and secondary caregivers. The good cooperation also demonstrates what can be achieved if efforts are focused and put into practice.

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Mouse parotid salivary gland organoids for the in vitro study of stem cell radiation response

Cited by 30 publications

References 48 publications

Current and Future Perspectives of the Use of Organoids in Radiobiology

Current and Future Perspectives of the Use of Organoids in Radiobiology

Oral Organoids: Progress and Challenges

Cooperation as core value in an innovative era

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