Perlecan Domain IV Peptide Stimulates Salivary Gland Cell Assembly<i>In Vitro</i>

Pradhan, Swati; Zhang, Chu; Jia, Xinqiao; Carson, Daniel D.; Witt, Robert L.; Farach-Carson, Mary C.

doi:10.1089/ten.tea.2008.0669

Cited by 43 publications

(54 citation statements)

References 25 publications

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“…Previously, we reported the isolation of human salivary acinar cells that self-assemble into acinilike structures and express salivary biomarkers when cultured on ECM derived human-compatible biomimetic peptides. 30 To better mimic the in vivo environment, we developed an HA-based, 2.5D hydrogel culture system that can support the growth and partial differentiation of 3D acini-like structures in vitro, but cannot be used to encapsulate cells. 6 We now report conversion of our 2.5D model to a fully 3D culture system that promotes organized growth and differentiation of FIG.…”

Section: Discussionmentioning

confidence: 99%

“…Homogeneous populations of proliferating acinar-like cells were obtained from tissue explant outgrowths and tissue dissociation procedures as previously described. 6,30 Parotid gland tissue specimens were minced to a slurry that was suspended in serum-free Hepato-STIMÔ medium (BD Biosciences Discovery Labware) and distributed in a six-well plate (BD FalconÔ) and left untouched for 7 days, and then supplemented with Hepato-STIMÔ growth medium until cells migrated out of the tissue explants. Confluent cells were passaged with 0.05% (w/v) trypsin EDTA (Invitrogen).…”

Section: Cell Culturementioning

confidence: 99%

“…30 Briefly, tissue cryosections (8 mm) were fixed with cold 100% methanol, rehydrated with 1 · PBS, and blocked overnight in 3% (w/v) bovine serum albumin (BSA) in PBS. Sections were incubated with primary antibody at 37°C for 45 min and washed in 1 · PBS for 30 min.…”

Section: Immunofluorescencementioning

confidence: 99%

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Implantable Three-Dimensional Salivary Spheroid Assemblies Demonstrate Fluid and Protein Secretory Responses to Neurotransmitters

Pradhan-Bhatt

Harrington

Duncan

et al. 2013

Tissue Engineering Part A

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Radiation treatment in patients with head and neck tumors commonly results in hyposalivation and xerostomia due to the loss of fluid-secreting salivary acinar cells. Patients develop susceptibility to oral infections, dental caries, impaired speech and swallowing, reducing the quality of life. Clinical management is largely unsatisfactory. The development of a tissue-engineered, implantable salivary gland will greatly benefit patients suffering from xerostomia. This report compares the ability of a 2.5-dimensional (2.5D) and a three-dimensional (3D) hyaluronic acid (HA)-based culture system to support functional salivary units capable of producing fluid and phenotypic proteins. Parotid cells seeded on 2.5D, as well as those encapsulated in 3D HA hydrogels, selfassembled into acini-like structures and expressed functional neurotransmitter receptors. Structures in 3D hydrogels merged to form organized 50 mm spheroids that could be maintained in culture for over 100 days and merged to form structures over 500 mm in size. Treatment of acini-like structures with the b-adrenergic agonists norepinephrine or isoproterenol increased granule production and a-amylase staining in treated structures, demonstrating regain of protein secretion. Upon treatment with the M3 muscarinic agonist acetylcholine, acinilike structures activated the fluid production pathway by increasing intracellular calcium levels. The increase in intracellular calcium seen in structures in the 3D hydrogel culture system was more robust and prolonged than that in 2.5D. To compare the long-term survival and retention of acini-like structures in vivo, cell-seeded 2.5D and 3D hydrogels were implanted into an athymic rat model. Cells in 2.5D failed to maintain organized acinilike structures and dispersed in the surrounding tissue. Encapsulated cells in 3D retained their spheroid structure and structural integrity, along with the salivary biomarkers and maintained viability for over 3 weeks in vivo. This report identifies a novel hydrogel culture system capable of creating and maintaining functional 3D salivary spheroid structures for long periods in vitro that regain both fluid and protein secreting functions and are suitable for tissue restoration.

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Section: Discussionmentioning

confidence: 99%

Section: Cell Culturementioning

confidence: 99%

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Implantable Three-Dimensional Salivary Spheroid Assemblies Demonstrate Fluid and Protein Secretory Responses to Neurotransmitters

Pradhan-Bhatt

Harrington

Duncan

et al. 2013

Tissue Engineering Part A

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“…Isolated embryonic salivary gland epithelial cells, or a mixture of epithelial and mesenchymal cells, can in fact readily self-assemble into bud-like structures that closely resemble normal developing salivary tissue and can even synthesize salivary gland differentiation markers (Wei et al, 2007). Gland branching or formation of acinar structures can be stimulated by biologically active peptides from laminin or perlecan (Pradhan et al, 2009;Kadoya and Yamashina, 2010), or by a biomaterial such as chitosan (Yang and Young, 2009). However, one uncertainty about this developmental recapitulation approach involves the question of how to establish the ductal system.…”

Section: Steps Toward Salivary Gland Reconstitution or Replacementmentioning

confidence: 99%

Dynamics of Salivary Gland Morphogenesis

2011

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A supplemental appendix to this article is published electronically only at http://jdr.sagepub.com/supplemental. AbstrAct Salivary glands form during embryonic development by a complex process that creates compact, highly organized secretory organs with functions essential for oral health. The architecture of these glands is generated by branching morphogenesis, revealed by recent research to involve unexpectedly dynamic cell motility and novel regulatory pathways. Numerous growth factors, extracellular matrix molecules, gene regulatory pathways, and mechanical forces contribute to salivary gland morphogenesis, but local gene regulation and morphological changes appear to play particularly notable roles. Here we review these recent advances and their potential application to salivary gland tissue engineering.

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“…Several research groups have incorporated basement membrane components into scaffolds developed to biochemically mimic the native ECM of the glands and promising results were obtained [14–18]. Laminin [14–15], perlecan peptide [16–17], fibronectin and collagen [18] were utilized for salivary cell regeneration [14–18]. However, the potential utility for elastin in scaffolds to advance salivary gland tissue engineering strategies has not been examined.…”

Section: Introductionmentioning

confidence: 99%

Elastin-PLGA hybrid electrospun nanofiber scaffolds for salivary epithelial cell self-organization and polarization

et al. 2017

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Development of electrospun nanofibers that mimic the structural, mechanical and biochemical properties of natural extracellular matrices (ECMs) is a promising approach for tissue regeneration. Electrospun fibers of synthetic polymers partially mimic the topography of the ECM, however, their high stiffness, poor hydrophilicity and lack of in vivo-like biochemical cues is not optimal for epithelial cell self-organization and function. In search of a biomimetic scaffold for salivary gland tissue regeneration, we investigated the potential of elastin, an ECM protein, to generate elastin hybrid nanofibers that have favorable physical and biochemical properties for regeneration of the salivary glands. Elastin was introduced to our previously developed poly-lactic-co-glycolic acid (PLGA) nanofiber scaffolds by two methods, blend electrospinning (EP-blend) and covalent conjugation (EP-covalent). Both methods for elastin incorporation into the nanofibers improved the wettability of the scaffolds while only blend electrospinning of elastin-PLGA nanofibers and not surface conjugation of elastin to PLGA fibers, conferred increased elasticity to the nanofibers measured by Young’s modulus. After two days, only the blend electrospun nanofiber scaffolds facilitated epithelial cell self-organization into cell clusters, assessed with nuclear area and nearest neighbor distance measurements, leading to the apicobasal polarization of salivary gland epithelial cells after six days, which is vital for cell function. This study suggests that elastin electrospun nanofiber scaffolds have potential application in regenerative therapies for salivary glands and other epithelial organs.

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Perlecan Domain IV Peptide Stimulates Salivary Gland Cell AssemblyIn Vitro

Cited by 43 publications

References 25 publications

Implantable Three-Dimensional Salivary Spheroid Assemblies Demonstrate Fluid and Protein Secretory Responses to Neurotransmitters

Implantable Three-Dimensional Salivary Spheroid Assemblies Demonstrate Fluid and Protein Secretory Responses to Neurotransmitters

Dynamics of Salivary Gland Morphogenesis

Elastin-PLGA hybrid electrospun nanofiber scaffolds for salivary epithelial cell self-organization and polarization

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