Bioinspired Precision Engineering of Three-Dimensional Epithelial Stem Cell Microniches.
cornea
differentiation
limbal stem cells
stem cell niche
two-photon polymerization
Journal
Advanced biosystems
ISSN: 2366-7478
Titre abrégé: Adv Biosyst
Pays: Germany
ID NLM: 101711718
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
20
01
2020
revised:
22
03
2020
accepted:
31
03
2020
pubmed:
25
4
2020
medline:
12
8
2021
entrez:
25
4
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32329968
doi: 10.1002/adbi.202000016
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2000016Subventions
Organisme : Medical Research Council
ID : MR/R015651/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/L013827/1)
Pays : United Kingdom
Organisme : Medical Research Council
ID : EP/L015072/1
Pays : United Kingdom
Informations de copyright
© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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