Ascl3 marks adult progenitor cells of the mouse salivary gland

Rugel-Stahl, Anastasia; Elliott, Marilyn; Ovitt, Catherine E.

doi:10.1016/j.scr.2012.01.002

Cited by 47 publications

(45 citation statements)

References 34 publications

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“…The SMG cell population is heterogeneous and consists of terminally differentiated cells, many of which undergo apoptosis after isolation. 8,10 However, the process of apoptosis takes *3 h, 78 which is in stark contrast to the *60-80% of SMG cell death observed after only minutes of exposure to chain-addition polymerizations (Fig. 1B).…”

Section: Resultsmentioning

confidence: 79%

“…After 2-3 days of suspension culture, dissociated SMG cells form microsphere cell clusters ( > 50 mm in diameter) that include both duct and acinar cells. 8,10 The viability of microspheres encapsulated within thiol-ene polymerized PEG hydrogels was analyzed using LIVE/DEAD imaging at days 0, 4, 7, and 14 after encapsulation (Fig. 5A-F) and by measuring whole hydrogel cellular ATP levels (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Primary mouse SMG cells were isolated as previously described. 8 Briefly, female C57BL/6 mice aged 8-24 weeks were euthanized according to animal protocols approved by the University of Rochester University Committee for Animal Resources. SMGs were surgically removed, finely minced with a razor blade, and dissociated by incubation in 5 mL Hank's Balanced Salt Solution (GIBCO) with CaCl 2 and MgCl 2, 1 mg/mL collagenase Type II (GIBCO), and 5 mg/mL hyaluronidase (Applichem) at 37°C for 40 min with gentle shaking.…”

Section: Cell Culturementioning

confidence: 99%

“…reports. 8,10 To directly track the fate of acinar cells within the hydrogels, a CreLoxP-ROSA26 lineage tracing system was used. In this system, an inducible Cre recombinase has been introduced into the Mist1 gene locus, which encodes a transcription factor specifically expressed in the secretory acinar cells.…”

Section: Figmentioning

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.…”

mentioning

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: Resultsmentioning

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Section: Cell Culturementioning

confidence: 99%

Section: Figmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Development of Poly(Ethylene Glycol) Hydrogels for Salivary Gland Tissue Engineering Applications

Shubin

Felong

Graunke

et al. 2015

Tissue Engineering Part A

Self Cite

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show abstract

Salivary gland stem cells: A review of development, regeneration and cancer

Emmerson

Knox

2018

Genesis

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Salivary glands are responsible for maintaining the health of the oral cavity and are routinely damaged by therapeutic radiation for head and neck cancer as well as by autoimmune diseases such as Sjögren's syndrome. Regenerative approaches based on the reactivation of endogenous stem cells or the transplant of exogenous stem cells hold substantial promise in restoring the structure and function of these organs to improve patient quality of life. However, these approaches have been hampered by a lack of knowledge on the identity of salivary stem cell populations and their regulators. In this review we discuss our current knowledge on salivary stem cells and their regulators during organ development, homeostasis and regeneration. As increasing evidence in other systems suggests that progenitor cells may be a source of cancer, we also review whether these same salivary stem cells may also be cancer initiating cells.

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Concise Review: Adult Salivary Gland Stem Cells and a Potential Therapy for Xerostomia

2013

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The ability to speak, swallow, masticate, taste food, and maintain a healthy oral cavity is heavily reliant on the presence of saliva, the hugely important effect of which on our everyday lives is often unappreciated. Hyposalivation, frequently experienced by people receiving radiation therapy for head and neck cancers, results in a plethora of symptoms whose combined effect can drastically reduce quality of life. Although artificial lubricants and drugs stimulating residual function are available to ameliorate the consequences of hyposalivation, their effects are at best transient. Such management techniques do not address the source of the problem: a lack of functional saliva-producing acinar cells, resulting from radiation-induced stem cell sterilization. Post-radiotherapy stimulation of cell proliferation only results in improved saliva secretion when part of the tissue has been spared or when the dose to the salivary gland (SG) remains below a certain level. Therefore, stem cell replacement therapy may be a good option to treat radiation-induced hyposalivation. Substantial progress has been made lately in the understanding of cell turnover in the SG, and the recent identification of stem and progenitor cell populations in the SG provides a basis for studies toward development of a stem cell-based therapy for xerostomia. Here, we review the current state of knowledge of SG stem cells and their potential for use in a cell-based therapy that may provide a more durable cure for hyposalivation.

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Ascl3 marks adult progenitor cells of the mouse salivary gland

Cited by 47 publications

References 34 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

Salivary gland stem cells: A review of development, regeneration and cancer

Concise Review: Adult Salivary Gland Stem Cells and a Potential Therapy for Xerostomia

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