Cell Sheets Restore Secretory Function in Wounded Mouse Submandibular Glands

Thermoresponsive cell culture plates release cells as confluent living sheets in response to small changes in temperature, with recovered cell sheets retaining functional extracellular matrix proteins and tight junctions, both of which indicate formation of intact and functional tissue. Our recent s...

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Main Authors: Harim T. dos Santos, Kyungsook Kim, Teruo Okano, Jean M. Camden, Gary A. Weisman, Olga J. Baker, Kihoon Nam
Format: Article
Language:English
Published: MDPI AG 2020-12-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/9/12/2645
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author Harim T. dos Santos
Kyungsook Kim
Teruo Okano
Jean M. Camden
Gary A. Weisman
Olga J. Baker
Kihoon Nam
author_facet Harim T. dos Santos
Kyungsook Kim
Teruo Okano
Jean M. Camden
Gary A. Weisman
Olga J. Baker
Kihoon Nam
author_sort Harim T. dos Santos
collection DOAJ
description Thermoresponsive cell culture plates release cells as confluent living sheets in response to small changes in temperature, with recovered cell sheets retaining functional extracellular matrix proteins and tight junctions, both of which indicate formation of intact and functional tissue. Our recent studies demonstrated that cell sheets are highly effective in promoting mouse submandibular gland (SMG) cell differentiation and recovering tissue integrity. However, these studies were performed only at early time points and extension of the observation period is needed to investigate duration of the cell sheets. Thus, the goal of this study was to demonstrate that treatment of wounded mouse SMG with cell sheets is capable of increasing salivary epithelial integrity over extended time periods. The results indicate that cell sheets promote tissue organization as early as eight days after transplantation and that these effects endure through Day 20. Furthermore, cell sheet transplantation in wounded SMG induces a significant time-dependent enhancement of cell polarization, differentiation and ion transporter expression. Finally, this treatment restored saliva quantity to pre-wounding levels at both eight and twenty days post-surgery and significantly improved saliva quality at twenty days post-surgery. These data indicate that cell sheets engineered with thermoresponsive cell culture plates are useful for salivary gland regeneration and provide evidence for the long-term stability of cell sheets, thereby offering a potential new therapeutic strategy for treating hyposalivation.
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spelling doaj.art-b8a2b1faa4034a1f953838d874b459712023-11-21T00:00:29ZengMDPI AGCells2073-44092020-12-01912264510.3390/cells9122645Cell Sheets Restore Secretory Function in Wounded Mouse Submandibular GlandsHarim T. dos Santos0Kyungsook Kim1Teruo Okano2Jean M. Camden3Gary A. Weisman4Olga J. Baker5Kihoon Nam6Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USACell Sheet Tissue Engineering Center (CSTEC), Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USACell Sheet Tissue Engineering Center (CSTEC), Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USAChristopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USAChristopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USAChristopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USAChristopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USAThermoresponsive cell culture plates release cells as confluent living sheets in response to small changes in temperature, with recovered cell sheets retaining functional extracellular matrix proteins and tight junctions, both of which indicate formation of intact and functional tissue. Our recent studies demonstrated that cell sheets are highly effective in promoting mouse submandibular gland (SMG) cell differentiation and recovering tissue integrity. However, these studies were performed only at early time points and extension of the observation period is needed to investigate duration of the cell sheets. Thus, the goal of this study was to demonstrate that treatment of wounded mouse SMG with cell sheets is capable of increasing salivary epithelial integrity over extended time periods. The results indicate that cell sheets promote tissue organization as early as eight days after transplantation and that these effects endure through Day 20. Furthermore, cell sheet transplantation in wounded SMG induces a significant time-dependent enhancement of cell polarization, differentiation and ion transporter expression. Finally, this treatment restored saliva quantity to pre-wounding levels at both eight and twenty days post-surgery and significantly improved saliva quality at twenty days post-surgery. These data indicate that cell sheets engineered with thermoresponsive cell culture plates are useful for salivary gland regeneration and provide evidence for the long-term stability of cell sheets, thereby offering a potential new therapeutic strategy for treating hyposalivation.https://www.mdpi.com/2073-4409/9/12/2645cell sheetextracellular matrixhyposalivationregenerationwound healing
spellingShingle Harim T. dos Santos
Kyungsook Kim
Teruo Okano
Jean M. Camden
Gary A. Weisman
Olga J. Baker
Kihoon Nam
Cell Sheets Restore Secretory Function in Wounded Mouse Submandibular Glands
Cells
cell sheet
extracellular matrix
hyposalivation
regeneration
wound healing
title Cell Sheets Restore Secretory Function in Wounded Mouse Submandibular Glands
title_full Cell Sheets Restore Secretory Function in Wounded Mouse Submandibular Glands
title_fullStr Cell Sheets Restore Secretory Function in Wounded Mouse Submandibular Glands
title_full_unstemmed Cell Sheets Restore Secretory Function in Wounded Mouse Submandibular Glands
title_short Cell Sheets Restore Secretory Function in Wounded Mouse Submandibular Glands
title_sort cell sheets restore secretory function in wounded mouse submandibular glands
topic cell sheet
extracellular matrix
hyposalivation
regeneration
wound healing
url https://www.mdpi.com/2073-4409/9/12/2645
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