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A novel in vivo model for evaluating functional restoration of a tissue-engineered salivary gland

Authors

  • Swati Pradhan-Bhatt PhD,

    1. Department of Biological Sciences, Biomedical Engineering Program, University of Delaware, Newark, Delaware
    2. Department of Materials Sciences and Engineering, Biomedical Engineering Program , University of Delaware, Newark, Delaware
    3. Department of Otolaryngology–Head and Neck Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A.
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  • Daniel A. Harrington PhD,

    1. Department of Biochemistry and Cell Biology, Rice University, Houston, Texas
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  • Randall L. Duncan PhD,

    1. Department of Biological Sciences, Biomedical Engineering Program, University of Delaware, Newark, Delaware
    2. Department of Materials Sciences and Engineering, Biomedical Engineering Program , University of Delaware, Newark, Delaware
    3. Department of Otolaryngology–Head and Neck Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A.
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  • Mary C. Farach-Carson PhD,

    1. Department of Biological Sciences, Biomedical Engineering Program, University of Delaware, Newark, Delaware
    2. Department of Materials Sciences and Engineering, Biomedical Engineering Program , University of Delaware, Newark, Delaware
    3. Helen F. Graham Cancer Center, Christiana Care, Newark, Delaware
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  • Xinqiao Jia PhD,

    1. the Center for Translational Cancer Research, Biomedical Engineering Program, University of Delaware, Newark, Delaware
    2. Department of Biochemistry and Cell Biology, Rice University, Houston, Texas
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  • Robert L. Witt MD

    Corresponding author
    1. Department of Biological Sciences, Biomedical Engineering Program, University of Delaware, Newark, Delaware
    2. the Center for Translational Cancer Research, Biomedical Engineering Program, University of Delaware, Newark, Delaware
    3. Helen F. Graham Cancer Center, Christiana Care, Newark, Delaware
    4. Department of Otolaryngology–Head and Neck Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A.
    • Send correspondence to Robert L. Witt, MD, Helen F. Graham Cancer Center, Christiana Care, 4745 Ogletown-Stanton Road, MAP #1, Suite 112, Newark, DE 19713. E-mail: robertlwitt@gmail.com

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Errata

This article is corrected by:

  1. Errata: Erratum Article first published online: 30 June 2016

  • Presented at the Triological Society 116th Annual Meeting at COSM, Orlando, Florida, U.S.A., April 10–14, 2013.

  • This work was supported by a private philanthropic contribution, and NIH/DE R01 DE022386, NIH/NCI P01-CA098912, and COBRE P20-RR016458 grants.

  • The authors have no other funding, financial relationships, or conflicts of interest to disclose.

Abstract

Objectives/Hypothesis

To create a novel model for development of a tissue-engineered salivary gland from human salivary gland cells that retains progenitor cell markers useful for treatment of radiation-induced xerostomia.

Study Design

A three-dimensional (3D) hyaluronic acid (HA)-based hydrogel scaffold was used to encapsulate primary human salivary gland cells and to obtain organized acini-like spheroids. Hydrogels were implanted into rat models, and cell viability and receptor expression were evaluated.

Methods

A parotid gland surgical resection model for xenografting was developed. Salivary cells loaded in HA hydrogels formed spheroids and in vitro were implanted in the three-fourths resected parotid bed of athymic rats. Implants were removed after 1 week and analyzed for spheroid viability and phenotype retention.

Results

Spheroids in 3D stained positive for HA receptors CD168/RHAMM and CD44, which is also a progenitor cell marker. The parotid gland three-fourths resection model was well-tolerated by rodent hosts, and the salivary cell/hydrogel scaffolds were adherent to the remaining parotid gland, with no obvious signs of inflammation. A majority of human cells in the extracted hydrogels demonstrated robust expression of CD44.

Conclusions

A 3D HA-based hydrogel scaffold that supported long-term culture of salivary gland cells into organized spheroids was established. An in vivo salivary gland resection model was developed that allowed for integration of the 3D HA hydrogel scaffold with the existing glandular parenchyma. The expression of CD44 among salivary cultures may partially explain their regenerative potential, and the expression of CD168/RHAMM along with CD44 may aid the development of these 3D spheroids into regenerated salivary glands

Level of Evidence

NA Laryngoscope, 124:456–461, 2014

Ancillary