Stem Cell–Soluble Signals Enhance Multilumen Formation in SMG Cell Clusters

Maruyama, Christina L.; Leigh, Noel J.; Nelson, James W.; McCall, Andrew D.; Mellas, Rachel E.; Lei, Pedro; Andreadis, Stelios T.; Baker, Olga J.

doi:10.1177/0022034515600157

Cited by 29 publications

(28 citation statements)

References 38 publications

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“…44 Cch (100 µM) induced an increase in [Ca 2+ ] i in Par-C10 cells cultured under all the conditions studied (i.e., FH, SGIYR, RAD, YIGSR, A99 alone and in combination, Figure 5A–F), consistent with results from previous studies using rat parotid gland and Par-C10 cells. 8,20 However, Par-C10 cells cultured on YIGSR-modified FH (Figure 5B,G) displayed a significantly higher increase of [Ca 2+ ] i as compared to unmodified FH (Figure 5A,G) and A99-modified FH (Figure 5C,G). Furthermore, increases of [Ca 2+ ] i in Par-C10 cells on FH containing both YIGSR and A99 peptides (Figure 5D,G) was significantly different from the [Ca 2+ ] i response observed on FH modified with YIGSR alone.…”

Section: Resultsmentioning

confidence: 93%

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Laminin-111 Peptides Conjugated to Fibrin Hydrogels Promote Formation of Lumen Containing Parotid Gland Cell Clusters

et al. 2016

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Previous studies showed that mouse submandibular gland cells form three-dimensional structures when grown on Laminin-111 gels. The use of Laminin-111 for tissue bioengineering is complicated due to its lack of purity. By contrast, the use of synthetic peptides derived from Laminin-111 is beneficial due to their high purity and easy manipulation. Two Laminin-111 peptides have been identified for salivary cells: the A99 peptide corresponding to the α1 chain from Laminin-111 and the YIGSR peptide corresponding to the β1 chain from Laminin-111, which are important for cell adhesion and migration. We created three-dimensional salivary cell clusters using a modified fibrin hydrogel matrix containing immobilized Laminin-111 peptides. Results indicate that the YIGSR peptide improved morphology and lumen formation in rat parotid Par-C10 cells as compared to cells grown on unmodified fibrin hydrogel. Moreover, a combination of both peptides not only allowed the formation of functional three-dimensional salivary cell clusters but also increased attachment and number of cell clusters. In summary, we demonstrated that fibrin hydrogel decorated with Laminin-111 peptides supports attachment and differentiation of salivary gland cell clusters with mature lumens.

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Section: Resultsmentioning

confidence: 93%

“…These results are relevant to both human and mouse studies, as previous studies showed that both of these cell types form 3D salivary cell clusters when grown on different scaffolds, such as Matrigel or L1. 20,42,43 …”

Section: Resultsmentioning

confidence: 99%

Laminin-111 Peptides Conjugated to Fibrin Hydrogels Promote Formation of Lumen Containing Parotid Gland Cell Clusters

et al. 2016

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“…Additionally, laminin was incorporated into the macromer solutions at 0.1 mg/mL due to previous studies highlighting the efficacy of laminin in both salivary gland regeneration and tissue engineering approaches [27,28,51–53]. Briefly, SMG sphere cell number was determined using a hemocytometer.…”

Section: Methodsmentioning

confidence: 99%

Encapsulation of primary salivary gland cells in enzymatically degradable poly(ethylene glycol) hydrogels promotes acinar cell characteristics

et al. 2017

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Radiation therapy for head and neck cancers leads to permanent xerostomia due to the loss of secretory acinar cells in the salivary glands. Regenerative treatments utilizing primary submandibular gland (SMG) cells show modest improvements in salivary secretory function, but there is limited evidence of salivary gland regeneration. We have recently shown that poly(ethylene glycol) (PEG) hydrogels can support the survival and proliferation of SMG cells as multicellular spheres in vitro. To further develop this approach for cell-based salivary gland regeneration, we have investigated how different modes of PEG hydrogel degradation affect the proliferation, cell-specific gene expression, and epithelial morphology within encapsulated salivary gland spheres. Comparison of non-degradable, hydrolytically-degradable, matrix metalloproteinase (MMP)-degradable, and mixed mode-degradable hydrogels showed that hydrogel degradation by any mechanism is required for significant proliferation of encapsulated cells. The expression of acinar phenotypic markers Aqp5 and Nkcc1 was increased in hydrogels that are MMP-degradable compared with other hydrogel compositions. However, expression of secretory acinar proteins Mist1 and Pip was not maintained to the same extent as phenotypic markers, suggesting changes in cell function upon encapsulation. Nevertheless, MMP- and mixed mode-degradability promoted organization of polarized cell types forming tight junctions and expression of the basement membrane proteins laminin and collagen IV within encapsulated SMG spheres. This work demonstrates that cellularly remodeled hydrogels can promote proliferation and gland-like organization by encapsulated salivary gland cells as well as maintenance of acinar cell characteristics required for regenerative approaches. Investigation is required to identify approaches to further enhance acinar secretory properties.

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“…ZO-1 is expressed in acini, ducts, and inter-glandular endothelial cells from human major salivary glands and mouse submandibular glands 14,39,81 and is also co-localized with claudin-16 at the excretory duct of human major salivary glands. 81 ZO-1 has been used as a marker for salivary gland polarity and differentiation; 110 however, further studies are needed to determine the molecular mechanisms by which ZO-1 modulates TJs in salivary glands.…”

Section: Tight Junction Plaque Proteinsmentioning

confidence: 99%

“…Several recent studies have demonstrated that TJs can be formed from primary salivary in vitro, 110,[116][117][118][119] an advance which can be used to study barrier function of the salivary epithelium in a system that more closely resembles native tissue. Furthermore, the use of knockout mice for the various TJ proteins will also prove useful in determining the role of these proteins for in vivo salivary gland functioning.…”

Section: Models Available To Study Tight Junctions In Salivary Glandsmentioning

confidence: 99%

Current trends in salivary gland tight junctions

Baker

2016

Tissue Barriers

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Tight junctions form a continuous intercellular barrier between epithelial cells that is required to separate tissue spaces and regulate selective movement of solutes across the epithelium. They are composed of strands containing integral membrane proteins (e.g., claudins, occludin and tricellulin, junctional adhesion molecules and the coxsackie adenovirus receptor). These proteins are anchored to the cytoskeleton via scaffolding proteins such as ZO-1 and ZO-2. In salivary glands, tight junctions are involved in polarized saliva secretion and barrier maintenance between the extracellular environment and the glandular lumen. This review seeks to provide an overview of what is currently known, as well as the major questions and future research directions, regarding tight junction expression, organization and function within salivary glands.

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Stem Cell–Soluble Signals Enhance Multilumen Formation in SMG Cell Clusters

Cited by 29 publications

References 38 publications

Laminin-111 Peptides Conjugated to Fibrin Hydrogels Promote Formation of Lumen Containing Parotid Gland Cell Clusters

Laminin-111 Peptides Conjugated to Fibrin Hydrogels Promote Formation of Lumen Containing Parotid Gland Cell Clusters

Encapsulation of primary salivary gland cells in enzymatically degradable poly(ethylene glycol) hydrogels promotes acinar cell characteristics

Current trends in salivary gland tight junctions

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