Biofabrication of a Tubular Model of Human Urothelial Mucosa Using Human Wharton Jelly Mesenchymal Stromal Cells

Several models of bioartificial human urothelial mucosa (UM) have been described recently. In this study, we generated novel tubularized UM substitutes using alternative sources of cells. Nanostructured fibrin–agarose biomaterials containing fibroblasts isolated from the human ureter were used as st...

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Main Authors: Ingrid Garzón, Boris Damián Jaimes-Parra, Manrique Pascual-Geler, José Manuel Cózar, María del Carmen Sánchez-Quevedo, María Auxiliadora Mosquera-Pacheco, Indalecio Sánchez-Montesinos, Ricardo Fernández-Valadés, Fernando Campos, Miguel Alaminos
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:Polymers
Subjects:
Online Access:https://www.mdpi.com/2073-4360/13/10/1568
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author Ingrid Garzón
Boris Damián Jaimes-Parra
Manrique Pascual-Geler
José Manuel Cózar
María del Carmen Sánchez-Quevedo
María Auxiliadora Mosquera-Pacheco
Indalecio Sánchez-Montesinos
Ricardo Fernández-Valadés
Fernando Campos
Miguel Alaminos
author_facet Ingrid Garzón
Boris Damián Jaimes-Parra
Manrique Pascual-Geler
José Manuel Cózar
María del Carmen Sánchez-Quevedo
María Auxiliadora Mosquera-Pacheco
Indalecio Sánchez-Montesinos
Ricardo Fernández-Valadés
Fernando Campos
Miguel Alaminos
author_sort Ingrid Garzón
collection DOAJ
description Several models of bioartificial human urothelial mucosa (UM) have been described recently. In this study, we generated novel tubularized UM substitutes using alternative sources of cells. Nanostructured fibrin–agarose biomaterials containing fibroblasts isolated from the human ureter were used as stroma substitutes. Then, human Wharton jelly mesenchymal stromal cells (HWJSC) were used to generate an epithelial-like layer on top. Three differentiation media were used for 7 and 14 days. Results showed that the biofabrication methods used here succeeded in generating a tubular structure consisting of a stromal substitute with a stratified epithelial-like layer on top, especially using a medium containing epithelial growth and differentiation factors (EM), although differentiation was not complete. At the functional level, UM substitutes were able to synthesize collagen fibers, proteoglycans and glycosaminoglycans, although the levels of control UM were not reached ex vivo. Epithelial differentiation was partially achieved, especially with EM after 14 days of development, with expression of keratins 7, 8, and 13 and pancytokeratin, desmoplakin, tight-junction protein-1, and uroplakin 2, although at lower levels than controls. These results confirm the partial urothelial differentiative potential of HWJSC and suggest that the biofabrication methods explored here were able to generate a potential substitute of the human UM for future clinical use.
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spelling doaj.art-7397b5aedf9a48d69d7e9bf711cb14082023-11-21T19:37:34ZengMDPI AGPolymers2073-43602021-05-011310156810.3390/polym13101568Biofabrication of a Tubular Model of Human Urothelial Mucosa Using Human Wharton Jelly Mesenchymal Stromal CellsIngrid Garzón0Boris Damián Jaimes-Parra1Manrique Pascual-Geler2José Manuel Cózar3María del Carmen Sánchez-Quevedo4María Auxiliadora Mosquera-Pacheco5Indalecio Sánchez-Montesinos6Ricardo Fernández-Valadés7Fernando Campos8Miguel Alaminos9Tissue Engineering Group, Department of Histology, Faculty of Medicine, University of Granada, 18016 Granada, SpainTissue Engineering Group, Department of Histology, Faculty of Medicine, University of Granada, 18016 Granada, SpainDivision of Urology, University Hospital Virgen de las Nieves, 18014 Granada, SpainInstituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, SpainTissue Engineering Group, Department of Histology, Faculty of Medicine, University of Granada, 18016 Granada, SpainDivision of Gastroenterology, Julio Hooker Digest Center, Cali 760036, ColombiaInstituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, SpainInstituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, SpainTissue Engineering Group, Department of Histology, Faculty of Medicine, University of Granada, 18016 Granada, SpainTissue Engineering Group, Department of Histology, Faculty of Medicine, University of Granada, 18016 Granada, SpainSeveral models of bioartificial human urothelial mucosa (UM) have been described recently. In this study, we generated novel tubularized UM substitutes using alternative sources of cells. Nanostructured fibrin–agarose biomaterials containing fibroblasts isolated from the human ureter were used as stroma substitutes. Then, human Wharton jelly mesenchymal stromal cells (HWJSC) were used to generate an epithelial-like layer on top. Three differentiation media were used for 7 and 14 days. Results showed that the biofabrication methods used here succeeded in generating a tubular structure consisting of a stromal substitute with a stratified epithelial-like layer on top, especially using a medium containing epithelial growth and differentiation factors (EM), although differentiation was not complete. At the functional level, UM substitutes were able to synthesize collagen fibers, proteoglycans and glycosaminoglycans, although the levels of control UM were not reached ex vivo. Epithelial differentiation was partially achieved, especially with EM after 14 days of development, with expression of keratins 7, 8, and 13 and pancytokeratin, desmoplakin, tight-junction protein-1, and uroplakin 2, although at lower levels than controls. These results confirm the partial urothelial differentiative potential of HWJSC and suggest that the biofabrication methods explored here were able to generate a potential substitute of the human UM for future clinical use.https://www.mdpi.com/2073-4360/13/10/1568urothelial mucosahuman Wharton jelly mesenchymal stromal cellsbiofabrication
spellingShingle Ingrid Garzón
Boris Damián Jaimes-Parra
Manrique Pascual-Geler
José Manuel Cózar
María del Carmen Sánchez-Quevedo
María Auxiliadora Mosquera-Pacheco
Indalecio Sánchez-Montesinos
Ricardo Fernández-Valadés
Fernando Campos
Miguel Alaminos
Biofabrication of a Tubular Model of Human Urothelial Mucosa Using Human Wharton Jelly Mesenchymal Stromal Cells
Polymers
urothelial mucosa
human Wharton jelly mesenchymal stromal cells
biofabrication
title Biofabrication of a Tubular Model of Human Urothelial Mucosa Using Human Wharton Jelly Mesenchymal Stromal Cells
title_full Biofabrication of a Tubular Model of Human Urothelial Mucosa Using Human Wharton Jelly Mesenchymal Stromal Cells
title_fullStr Biofabrication of a Tubular Model of Human Urothelial Mucosa Using Human Wharton Jelly Mesenchymal Stromal Cells
title_full_unstemmed Biofabrication of a Tubular Model of Human Urothelial Mucosa Using Human Wharton Jelly Mesenchymal Stromal Cells
title_short Biofabrication of a Tubular Model of Human Urothelial Mucosa Using Human Wharton Jelly Mesenchymal Stromal Cells
title_sort biofabrication of a tubular model of human urothelial mucosa using human wharton jelly mesenchymal stromal cells
topic urothelial mucosa
human Wharton jelly mesenchymal stromal cells
biofabrication
url https://www.mdpi.com/2073-4360/13/10/1568
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