Encapsulation of Primary Salivary Gland Acinar Cell Clusters and Intercalated Ducts (AIDUCs) within Matrix Metalloproteinase (MMP)‐Degradable Hydrogels to Maintain Tissue Structure and Function

Song, Youhong; Sharipol, Azmeer; Uchida, Hitoshi; Ingalls, Matthew H.; Piraino, Lindsay; Mereness, Jared A.; Moyston, Tracey; DeLouise, Lisa A.; Ovitt, Catherine E.; Benoit, Danielle S. W.

doi:10.1002/adhm.202101948

Cited by 10 publications

(14 citation statements)

References 99 publications

(167 reference statements)

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“…Cells were centrifuged, then resuspended in HBSS with 15 mM HEPES and passed through 100 μm and 20 μm mesh filters to isolate clusters between 20-100 μm. The digestion protocol produces cell cluster sizes evenly distributed between 20 to 100 μm [33]. The isolated clusters were combined with hydrogel precursor solution and seeded in MB array-based chips as described below.…”

Section: Methodsmentioning

confidence: 99%

Radioprotective drug screening in a salivary gland tissue chip

Piraino

Chen

Mereness

et al. 2023

Preprint

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Ionizing radiation damage to the salivary glands during head and neck cancer treatment often causes a permanent loss of secretory function. Due to the resulting decrease in saliva production, patients experience difficulty with eating, speaking, and swallowing and are predisposed to oral infections and tooth decay. While the radioprotective drug amifostine is approved to prevent radiation-induced hyposalivation, it has intolerable side effects that limit its use and motivate research into discovering alternatives. To address this issue, we have developed a salivary gland mimetic (SGm) tissue chip platform for use in high-content drug discovery. Here, we report on the development and validation of in-chip assays to quantify reduced glutathione and cellular senescence (β-galactosidase) as measures of radiation damage and protection using WR-1065, the active form of amifostine. Following validation, we next tested our assays using other reported radioprotective drugs including Edaravone, Tempol, N-acetylcysteine, Rapamycin, Ex-Rad, and Palifermin. The validated assays were then used to screen a library of FDA-approved compounds for radioprotection. We screened 438 compounds, obtained 25 hits that were further tested for EC50 values and downselected using information from the PubChem database. Lead compounds were identified that are being tested in preclinical models.

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Section: Methodsmentioning

confidence: 99%

Radioprotective drug screening in a salivary gland tissue chip

Piraino

Chen

Mereness

et al. 2023

Preprint

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“…Dispersed SMG clusters were subsequently passed through 100 and 20 μm filters to isolate clusters between 20–100 µm. The digestion protocol produces cell cluster sizes evenly distributed between 20 to 100 µm [ 32 ]. The isolated clusters were re-suspended in base culture medium, defined below.…”

Section: Methodsmentioning

confidence: 99%

Optimizing Soluble Cues for Salivary Gland Tissue Mimetics Using a Design of Experiments (DoE) Approach

Piraino

Benoit

DeLouise

2022

Cells

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The development of therapies to prevent or treat salivary gland dysfunction has been limited by a lack of functional in vitro models. Specifically, critical markers of salivary gland secretory phenotype downregulate rapidly ex vivo. Here, we utilize a salivary gland tissue chip model to conduct a design of experiments (DoE) approach to test combinations of seven soluble cues that were previously shown to maintain or improve salivary gland cell function. This approach uses statistical techniques to improve efficiency and accuracy of combinations of factors. The DoE-designed culture conditions improve markers of salivary gland function. Data show that the EGFR inhibitor, EKI-785, maintains relative mRNA expression of Mist1, a key acinar cell transcription factor, while FGF10 and neurturin promote mRNA expression of Aqp5 and Tmem16a, channel proteins involved in secretion. Mist1 mRNA expression correlates with increased secretory function, including calcium signaling and mucin (PAS-AB) staining. Overall, this study demonstrates that media conditions can be efficiently optimized to support secretory function in vitro using a DoE approach.

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“…More recently, Song et encapsulation of primary SG acinar cell clusters and intercalated ducts (AIDUCs) in 3D hydrogels to form SG microtissues. 58 The authors reported that the cell clusters maintained key SG-specific markers like NKCC1, PIP, and AQP5 in 3D for 14 days in culture and responded to stimulation by purinergic agonists. 1.2.…”

Section: Understanding the Sg Cell Niche�sourcing And Isolation Strat...mentioning

confidence: 99%

Bioengineered Salivary Gland Microtissues─A Review of 3D Cellular Models and their Applications

Pillai,

Munguia-Lopez,

Tran

2024

ACS Appl. Bio Mater.

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Salivary glands (SGs) play a vital role in maintaining oral health through the production and release of saliva. Injury to SGs can lead to gland hypofunction and a decrease in saliva secretion manifesting as xerostomia. While symptomatic treatments for xerostomia exist, effective permanent solutions are still lacking, emphasizing the need for innovative approaches. Significant progress has been made in the field of three-dimensional (3D) SG bioengineering for applications in gland regeneration. This has been achieved through a major focus on cell culture techniques, including soluble cues and biomaterial components of the 3D niche. Cells derived from both adult and embryonic SGs have highlighted key in vitro characteristics of SG 3D models. While still in its first decade of exploration, SG spheroids and organoids have so far served as crucial tools to study SG pathophysiology. This review, based on a literature search over the past decade, covers the importance of SG cell types in the realm of their isolation, sourcing, and culture conditions that modulate the 3D microenvironment. We discuss different biomaterials employed for SG culture and the current advances made in bioengineering SG models using them. The success of these 3D cellular models are further evaluated in the context of their applications in organ transplantation and in vitro disease modeling.

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Encapsulation of Primary Salivary Gland Acinar Cell Clusters and Intercalated Ducts (AIDUCs) within Matrix Metalloproteinase (MMP)‐Degradable Hydrogels to Maintain Tissue Structure and Function

Cited by 10 publications

References 99 publications

Radioprotective drug screening in a salivary gland tissue chip

Radioprotective drug screening in a salivary gland tissue chip

Optimizing Soluble Cues for Salivary Gland Tissue Mimetics Using a Design of Experiments (DoE) Approach

Bioengineered Salivary Gland Microtissues─A Review of 3D Cellular Models and their Applications

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