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An inspired microenvironment of cell replicas to induce stem cells into keratocyte-like dendritic cells for corneal regeneration

Corneal stromal disorders due to the loss of keratocytes can affect visual impairment and blindness. Corneal cell therapy is a promising therapeutic strategy for healing corneal tissue or even enhancing corneal function upon advanced disorders, however, the sources of corneal keratocytes are limited...

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Autores principales: Fallah Tafti, Mahsa, Aghamollaei, Hossein, Moosazadeh Moghaddam, Mehrdad, Jadidi, Khosrow, Faghihi, Shahab
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10495344/
https://www.ncbi.nlm.nih.gov/pubmed/37696883
http://dx.doi.org/10.1038/s41598-023-42359-9
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author Fallah Tafti, Mahsa
Aghamollaei, Hossein
Moosazadeh Moghaddam, Mehrdad
Jadidi, Khosrow
Faghihi, Shahab
author_facet Fallah Tafti, Mahsa
Aghamollaei, Hossein
Moosazadeh Moghaddam, Mehrdad
Jadidi, Khosrow
Faghihi, Shahab
author_sort Fallah Tafti, Mahsa
collection PubMed
description Corneal stromal disorders due to the loss of keratocytes can affect visual impairment and blindness. Corneal cell therapy is a promising therapeutic strategy for healing corneal tissue or even enhancing corneal function upon advanced disorders, however, the sources of corneal keratocytes are limited for clinical applications. Here, the capacity of cell-imprinted substrates fabricated by molding human keratocyte templates to induce differentiation of human adipose-derived stem cells (hADSCs) into keratocytes, is presented. Keratocytes are isolated from human corneal stroma and grown to transmit their ECM architecture and cell-like topographies to a PDMS substrate. The hADSCs are then seeded on cell-imprinted substrates and their differentiation to keratocytes in DMEM/F12 (with and without chemical factors) are evaluated by real-time PCR and immunocytochemistry. The mesenchymal stem cells grown on patterned substrates present gene and protein expression profiles similar to corneal keratocytes. In contrast, a negligible expression of myofibroblast marker in the hADSCs cultivated on the imprinted substrates, is observed. Microscopic analysis reveals dendritic morphology and ellipsoid nuclei similar to primary keratocytes. Overall, it is demonstrated that biomimetic imprinted substrates would be a sufficient driver to solely direct the stem cell fate toward target cells which is a significant achievement toward corneal regeneration.
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spelling pubmed-104953442023-09-13 An inspired microenvironment of cell replicas to induce stem cells into keratocyte-like dendritic cells for corneal regeneration Fallah Tafti, Mahsa Aghamollaei, Hossein Moosazadeh Moghaddam, Mehrdad Jadidi, Khosrow Faghihi, Shahab Sci Rep Article Corneal stromal disorders due to the loss of keratocytes can affect visual impairment and blindness. Corneal cell therapy is a promising therapeutic strategy for healing corneal tissue or even enhancing corneal function upon advanced disorders, however, the sources of corneal keratocytes are limited for clinical applications. Here, the capacity of cell-imprinted substrates fabricated by molding human keratocyte templates to induce differentiation of human adipose-derived stem cells (hADSCs) into keratocytes, is presented. Keratocytes are isolated from human corneal stroma and grown to transmit their ECM architecture and cell-like topographies to a PDMS substrate. The hADSCs are then seeded on cell-imprinted substrates and their differentiation to keratocytes in DMEM/F12 (with and without chemical factors) are evaluated by real-time PCR and immunocytochemistry. The mesenchymal stem cells grown on patterned substrates present gene and protein expression profiles similar to corneal keratocytes. In contrast, a negligible expression of myofibroblast marker in the hADSCs cultivated on the imprinted substrates, is observed. Microscopic analysis reveals dendritic morphology and ellipsoid nuclei similar to primary keratocytes. Overall, it is demonstrated that biomimetic imprinted substrates would be a sufficient driver to solely direct the stem cell fate toward target cells which is a significant achievement toward corneal regeneration. Nature Publishing Group UK 2023-09-11 /pmc/articles/PMC10495344/ /pubmed/37696883 http://dx.doi.org/10.1038/s41598-023-42359-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Fallah Tafti, Mahsa
Aghamollaei, Hossein
Moosazadeh Moghaddam, Mehrdad
Jadidi, Khosrow
Faghihi, Shahab
An inspired microenvironment of cell replicas to induce stem cells into keratocyte-like dendritic cells for corneal regeneration
title An inspired microenvironment of cell replicas to induce stem cells into keratocyte-like dendritic cells for corneal regeneration
title_full An inspired microenvironment of cell replicas to induce stem cells into keratocyte-like dendritic cells for corneal regeneration
title_fullStr An inspired microenvironment of cell replicas to induce stem cells into keratocyte-like dendritic cells for corneal regeneration
title_full_unstemmed An inspired microenvironment of cell replicas to induce stem cells into keratocyte-like dendritic cells for corneal regeneration
title_short An inspired microenvironment of cell replicas to induce stem cells into keratocyte-like dendritic cells for corneal regeneration
title_sort inspired microenvironment of cell replicas to induce stem cells into keratocyte-like dendritic cells for corneal regeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10495344/
https://www.ncbi.nlm.nih.gov/pubmed/37696883
http://dx.doi.org/10.1038/s41598-023-42359-9
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