Alginate Hydrogel Microtubes for Salivary Gland Cell Organization and Cavitation

Understanding the different regulatory functions of epithelial and mesenchymal cell types in salivary gland development and cellular organization is essential for proper organoid formation and salivary gland tissue regeneration. Here, we demonstrate a biocompatible platform using pre-formed alginate...

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Main Authors: Matthew Jorgensen, Pujhitha Ramesh, Miriam Toro, Emily Evans, Nicholas Moskwa, Xulang Zhang, Susan T. Sharfstein, Melinda Larsen, Yubing Xie
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:Bioengineering
Subjects:
Online Access:https://www.mdpi.com/2306-5354/9/1/38
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author Matthew Jorgensen
Pujhitha Ramesh
Miriam Toro
Emily Evans
Nicholas Moskwa
Xulang Zhang
Susan T. Sharfstein
Melinda Larsen
Yubing Xie
author_facet Matthew Jorgensen
Pujhitha Ramesh
Miriam Toro
Emily Evans
Nicholas Moskwa
Xulang Zhang
Susan T. Sharfstein
Melinda Larsen
Yubing Xie
author_sort Matthew Jorgensen
collection DOAJ
description Understanding the different regulatory functions of epithelial and mesenchymal cell types in salivary gland development and cellular organization is essential for proper organoid formation and salivary gland tissue regeneration. Here, we demonstrate a biocompatible platform using pre-formed alginate hydrogel microtubes to facilitate direct epithelial–mesenchymal cell interaction for 3D salivary gland cell organization, which allows for monitoring cellular organization while providing a protective barrier from cell-cluster loss during medium changes. Using mouse salivary gland ductal epithelial SIMS cells as the epithelial model cell type and NIH 3T3 fibroblasts or primary E16 salivary mesenchyme cells as the stromal model cell types, self-organization from epithelial–mesenchymal interaction was examined. We observed that epithelial and mesenchymal cells undergo aggregation on day 1, cavitation by day 4, and generation of an EpCAM-expressing epithelial cell layer as early as day 7 of the co-culture in hydrogel microtubes, demonstrating the utility of hydrogel microtubes to facilitate heterotypic cell–cell interactions to form cavitated organoids. Thus, pre-formed alginate microtubes are a promising co-culture method for further understanding epithelial and mesenchymal interaction during tissue morphogenesis and for future practical applications in regenerative medicine.
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spelling doaj.art-d2e6efc7c64c4826881ee6d2baed7ca42023-11-23T12:59:27ZengMDPI AGBioengineering2306-53542022-01-01913810.3390/bioengineering9010038Alginate Hydrogel Microtubes for Salivary Gland Cell Organization and CavitationMatthew Jorgensen0Pujhitha Ramesh1Miriam Toro2Emily Evans3Nicholas Moskwa4Xulang Zhang5Susan T. Sharfstein6Melinda Larsen7Yubing Xie8College of Nanoscale Science and Engineering, SUNY Polytechnic Institute, 257 Fuller Road, Albany, NY 12203, USACollege of Nanoscale Science and Engineering, SUNY Polytechnic Institute, 257 Fuller Road, Albany, NY 12203, USACollege of Nanoscale Science and Engineering, SUNY Polytechnic Institute, 257 Fuller Road, Albany, NY 12203, USACollege of Nanoscale Science and Engineering, SUNY Polytechnic Institute, 257 Fuller Road, Albany, NY 12203, USADepartment of Biological Sciences, State University of New York, University at Albany, 1400 Washington Ave., Albany, NY 12222, USACollege of Nanoscale Science and Engineering, SUNY Polytechnic Institute, 257 Fuller Road, Albany, NY 12203, USACollege of Nanoscale Science and Engineering, SUNY Polytechnic Institute, 257 Fuller Road, Albany, NY 12203, USADepartment of Biological Sciences, State University of New York, University at Albany, 1400 Washington Ave., Albany, NY 12222, USACollege of Nanoscale Science and Engineering, SUNY Polytechnic Institute, 257 Fuller Road, Albany, NY 12203, USAUnderstanding the different regulatory functions of epithelial and mesenchymal cell types in salivary gland development and cellular organization is essential for proper organoid formation and salivary gland tissue regeneration. Here, we demonstrate a biocompatible platform using pre-formed alginate hydrogel microtubes to facilitate direct epithelial–mesenchymal cell interaction for 3D salivary gland cell organization, which allows for monitoring cellular organization while providing a protective barrier from cell-cluster loss during medium changes. Using mouse salivary gland ductal epithelial SIMS cells as the epithelial model cell type and NIH 3T3 fibroblasts or primary E16 salivary mesenchyme cells as the stromal model cell types, self-organization from epithelial–mesenchymal interaction was examined. We observed that epithelial and mesenchymal cells undergo aggregation on day 1, cavitation by day 4, and generation of an EpCAM-expressing epithelial cell layer as early as day 7 of the co-culture in hydrogel microtubes, demonstrating the utility of hydrogel microtubes to facilitate heterotypic cell–cell interactions to form cavitated organoids. Thus, pre-formed alginate microtubes are a promising co-culture method for further understanding epithelial and mesenchymal interaction during tissue morphogenesis and for future practical applications in regenerative medicine.https://www.mdpi.com/2306-5354/9/1/38alginatehydrogelmicrotube3D culturesalivary glandorganoids
spellingShingle Matthew Jorgensen
Pujhitha Ramesh
Miriam Toro
Emily Evans
Nicholas Moskwa
Xulang Zhang
Susan T. Sharfstein
Melinda Larsen
Yubing Xie
Alginate Hydrogel Microtubes for Salivary Gland Cell Organization and Cavitation
Bioengineering
alginate
hydrogel
microtube
3D culture
salivary gland
organoids
title Alginate Hydrogel Microtubes for Salivary Gland Cell Organization and Cavitation
title_full Alginate Hydrogel Microtubes for Salivary Gland Cell Organization and Cavitation
title_fullStr Alginate Hydrogel Microtubes for Salivary Gland Cell Organization and Cavitation
title_full_unstemmed Alginate Hydrogel Microtubes for Salivary Gland Cell Organization and Cavitation
title_short Alginate Hydrogel Microtubes for Salivary Gland Cell Organization and Cavitation
title_sort alginate hydrogel microtubes for salivary gland cell organization and cavitation
topic alginate
hydrogel
microtube
3D culture
salivary gland
organoids
url https://www.mdpi.com/2306-5354/9/1/38
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