Salisphere derived c-Kit+ cell transplantation restores tissue homeostasis in irradiated salivary gland

Nanduri, Lalitha S.Y.; Lombaert, Isabelle M.A.; Zwaag, Marianne van der; Faber, Hette; Brunsting, Jeanette F.; Os, Ronald P. van; Coppes, Robert P.

doi:10.1016/j.radonc.2013.05.020

Cited by 129 publications

(116 citation statements)

References 26 publications

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“…As in vitro culture of salivary gland cells under adherent conditions leads to loss of secretory cell characteristics and reduced proliferation, [101][102][103] we have adopted the use of microspheres, which have been shown to contribute to gland function after transplantation. 10,13 It is generally acknowledged that the maintenance and expansion of functional salivary gland cells requires a biomaterial scaffold. 21,24,104,105 Here, we have examined the feasibility of using PEG hydrogels.…”

Section: Figmentioning

confidence: 99%

“…[107][108][109] In previous studies, transplantation of primary SMG cells into irradiated glands was performed using intraglandular *5-10 mL injections. 10,12,13 We speculate that in situ polymerization of a hydrogel to surround damaged salivary glands may provide a direct means of delivering SMG cells for regeneration.…”

mentioning

confidence: 99%

“…[4][5][6] No salivary gland stem cell has been definitively identified as contributing to gland regeneration; however, several duct cell subtypes have been characterized as progenitor cells. [7][8][9][10][11][12] Furthermore, although the direct injection of progenitor cell populations, namely c-Kit + salivary progenitor cells 10,13 or mesenchymal stem cells (MSCs), 14 into irradiated submandibular glands (SMGs) showed some functional improvement, restoration of saliva secretion was incomplete, and highly variable. 13 To reproducibly promote regeneration and functional recovery of irradiated salivary glands, biomaterial-based approaches for cell transplantation have been explored.…”

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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: Figmentioning

confidence: 99%

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confidence: 99%

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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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“…In vitro salivary gland culture has also been attempted. The salispheres expressed salivary gland stem cell markers: CD24, CD29, CD34, CD44, CD49, CD90, and CD117 though maintaining pluripotency of acinar cells in culture is still a challenge 19 . Other upcoming methods would involve isolation of mesenchymal stem cells from bone marrow/adipose/epithelial tissues or from induced pluripotent stem (iPS) cells and inducing in vitro differentiation into salivary gland cells.…”

Section: Biologic and Surgicalmentioning

confidence: 99%

Radiation Induced Xerostomia: Current Concepts and Future Trends

Krishnan¹,

Iyer²,

Chakraborti³

et al. 2017

Def. Life. Sc. Jl.

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Radiation induced xerostomia is a persistent clinical presentation that affects the quality of life in head and neck cancer patients even with the best of the intensity modulated radiotherapy protocols. Comprehensive review of the anatomic, histologic, developmental and neuronal entities of salivary glands from a regenerative perspective, ensuing radiation is taken. It also evaluates the systemic and glandular radiation responses that form the early and late clinical changes. From these, the article submits probable strategies; based on the current knowledge and future challenges involved, in reversing radiation induced xerostomia. Further, it elaborates on the status of radioprotectors and mitigators including the recently reported biologic and chemical derivatives and proposes the rationale of using combination radioprotector therapy in radiation injuries. A brief of palliative regimes, alternate treatment modes and technologic advancements in radiotherapy are also explained. Salivary gland histologic components, which need to be protected in the emerging radiotherapy protocols and can be targeted in different salivary gland regeneration therapies is highlighted. The paper contributes to an improved understanding in radiation induced xerostomia and deliberates on novel mechanisms towards enhancing quality of life in head and neck cancer radiotherapy patients.

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“…al. [55] was able to show immune-histochemical staining of several stem cell markers in the ductal compartment of mouse submandibular glands including c-Kit, CD133, CD24, CD29, and CD49f. Interestingly, culturing gland cells as salispheres, enriches a c-Kit+ population after several days [56].…”

Section: Stem Cellsmentioning

confidence: 97%

A systems biology approach identifies a gene regulatory network in parotid acinar cell differentiation.

Metzler¹

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ACKNOWLEDGEMENTSThis study was undertaken with the help and support of many individuals. I would first like to thank my advisor Dr. Doug Darling who was always available for questions and advise, and whose continued support of myself and this project through difficult periods was essential and much appreciated. His guidance has helped me to develop as a scientist.I also worked closely with Dr. Srirangapatnam Venkatesh when I first started. His friendly and helpful attitude could always be counted on, and was wonderful to have during my initial training. He is greatly missed by all who knew him.

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Salisphere derived c-Kit+ cell transplantation restores tissue homeostasis in irradiated salivary gland

Abstract: Our results show that stem cell transplantation not only rescues hypo-salivation, but also restores tissue homeostasis of the irradiated gland, necessary for long-term maintenance of adult tissue.

Cited by 129 publications

References 26 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

Radiation Induced Xerostomia: Current Concepts and Future Trends

A systems biology approach identifies a gene regulatory network in parotid acinar cell differentiation.

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