Prina, E, Amer, MH orcid.org/0000-0002-1493-3181, Sidney, L et al. (10 more authors) (2020) Bioinspired Precision Engineering of Three‐Dimensional Epithelial Stem Cell Microniches. Advanced Biosystems, 4 (6). 2000016. ISSN 2366-7478
Abstract
Maintenance of the epithelium relies on stem cells residing within specialized microenvironments, known as epithelial crypts. Two‐photon polymerization (2PP) is a valuable tool for fabricating 3D micro/nanostructures for stem cell niche engineering applications. Herein, biomimetic gelatin methacrylate‐based constructs, replicating the precise geometry of the limbal epithelial crypt structures (limbal stem cell “microniches”) as an exemplar epithelial niche, are fabricated using 2PP. Human limbal epithelial stem cells (hLESCs) are seeded within the microniches in xeno‐free conditions to investigate their ability to repopulate the crypts and the expression of various differentiation markers. Cell proliferation and a zonation in cell phenotype along the z‐axis are observed without the use of exogenous signaling molecules. Significant differences in cell phenotype between cells located at the base of the microniche and those situated towards the rim are observed, demonstrating that stem cell fate is strongly influenced by its location within a niche and the geometrical details of where it resides. This study provides insight into the influence of the niche’s spatial geometry on hLESCs and demonstrates a flexible approach for the fabrication of biomimetic crypt‐like structures in epithelial tissues. This has significant implications for regenerative medicine applications and can ultimately lead to implantable synthetic “niche‐based” treatments.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | cornea; differentiation; limbal stem cells; stem cell niche; two‐photon polymerization |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 07 Jul 2020 14:14 |
Last Modified: | 07 Jul 2020 14:14 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/adbi.202000016 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:162893 |