Interfollicular epidermal stem-like cells for the recreation of the hair follicle epithelial compartment

Abstract Background Hair follicle (HF) development and growth are dependent on epithelial-mesenchymal interactions (EMIs). Dermal papilla (DP) cells are recognized as the key inductive mesenchymal player, but the ideal source of receptive keratinocytes for human HF regeneration is yet to be defined....

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Main Authors: Carla M. Abreu, Rogério P. Pirraco, Rui L. Reis, Mariana T. Cerqueira, Alexandra P. Marques
Format: Article
Language:English
Published: BMC 2021-01-01
Series:Stem Cell Research & Therapy
Subjects:
Online Access:https://doi.org/10.1186/s13287-020-02104-9
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author Carla M. Abreu
Rogério P. Pirraco
Rui L. Reis
Mariana T. Cerqueira
Alexandra P. Marques
author_facet Carla M. Abreu
Rogério P. Pirraco
Rui L. Reis
Mariana T. Cerqueira
Alexandra P. Marques
author_sort Carla M. Abreu
collection DOAJ
description Abstract Background Hair follicle (HF) development and growth are dependent on epithelial-mesenchymal interactions (EMIs). Dermal papilla (DP) cells are recognized as the key inductive mesenchymal player, but the ideal source of receptive keratinocytes for human HF regeneration is yet to be defined. We herein investigated whether human interfollicular epidermal keratinocytes with stem-like features (EpSlKCs), characterized by a α6bri/CD71dim expression, can replace human hair follicular keratinocytes (HHFKCs) for the recreation of the HF epithelium and respective EMIs. Methods The α6bri/CD71dim cellular fraction was selected from the whole interfollicular keratinocyte population through fluorescence-activated cell sorting and directly compared with follicular keratinocytes in terms of their proliferative capacity and phenotype. The crosstalk with DP cells was studied in an indirect co-culture system, and EpSlKC hair forming capacity tested in a hair reconstitution assay when combined with DP cells. Results EpSlKCs exhibited a phenotypic profile similar to follicular keratinocytes and were capable of increasing DP cell proliferation and, for short co-culture times, the number of alkaline phosphatase-active cells, suggesting an improvement of their inductivity. Moreover, the recreation of immature HFs and sebaceous glands was observed after EpSlKC and DP cell co-grafting in nude mice. Conclusions Our results suggest that EpSlKCs are akin to follicular keratinocytes and can crosstalk with DP cells, contributing to HF morphogenesis in vivo, thus representing an attractive epithelial cell source for hair regeneration strategies.
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spelling doaj.art-5ed16a7cf6184d30a40063d8ccac5ffa2023-10-22T11:07:56ZengBMCStem Cell Research & Therapy1757-65122021-01-0112111210.1186/s13287-020-02104-9Interfollicular epidermal stem-like cells for the recreation of the hair follicle epithelial compartmentCarla M. Abreu0Rogério P. Pirraco1Rui L. Reis2Mariana T. Cerqueira3Alexandra P. Marques43B’s Research Group – Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho3B’s Research Group – Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho3B’s Research Group – Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho3B’s Research Group – Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho3B’s Research Group – Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of MinhoAbstract Background Hair follicle (HF) development and growth are dependent on epithelial-mesenchymal interactions (EMIs). Dermal papilla (DP) cells are recognized as the key inductive mesenchymal player, but the ideal source of receptive keratinocytes for human HF regeneration is yet to be defined. We herein investigated whether human interfollicular epidermal keratinocytes with stem-like features (EpSlKCs), characterized by a α6bri/CD71dim expression, can replace human hair follicular keratinocytes (HHFKCs) for the recreation of the HF epithelium and respective EMIs. Methods The α6bri/CD71dim cellular fraction was selected from the whole interfollicular keratinocyte population through fluorescence-activated cell sorting and directly compared with follicular keratinocytes in terms of their proliferative capacity and phenotype. The crosstalk with DP cells was studied in an indirect co-culture system, and EpSlKC hair forming capacity tested in a hair reconstitution assay when combined with DP cells. Results EpSlKCs exhibited a phenotypic profile similar to follicular keratinocytes and were capable of increasing DP cell proliferation and, for short co-culture times, the number of alkaline phosphatase-active cells, suggesting an improvement of their inductivity. Moreover, the recreation of immature HFs and sebaceous glands was observed after EpSlKC and DP cell co-grafting in nude mice. Conclusions Our results suggest that EpSlKCs are akin to follicular keratinocytes and can crosstalk with DP cells, contributing to HF morphogenesis in vivo, thus representing an attractive epithelial cell source for hair regeneration strategies.https://doi.org/10.1186/s13287-020-02104-9Epidermal keratinocytes with stem-like featuresDermal papilla cellsEpithelial-mesenchymal interactionsHair follicleSebaceous gland
spellingShingle Carla M. Abreu
Rogério P. Pirraco
Rui L. Reis
Mariana T. Cerqueira
Alexandra P. Marques
Interfollicular epidermal stem-like cells for the recreation of the hair follicle epithelial compartment
Stem Cell Research & Therapy
Epidermal keratinocytes with stem-like features
Dermal papilla cells
Epithelial-mesenchymal interactions
Hair follicle
Sebaceous gland
title Interfollicular epidermal stem-like cells for the recreation of the hair follicle epithelial compartment
title_full Interfollicular epidermal stem-like cells for the recreation of the hair follicle epithelial compartment
title_fullStr Interfollicular epidermal stem-like cells for the recreation of the hair follicle epithelial compartment
title_full_unstemmed Interfollicular epidermal stem-like cells for the recreation of the hair follicle epithelial compartment
title_short Interfollicular epidermal stem-like cells for the recreation of the hair follicle epithelial compartment
title_sort interfollicular epidermal stem like cells for the recreation of the hair follicle epithelial compartment
topic Epidermal keratinocytes with stem-like features
Dermal papilla cells
Epithelial-mesenchymal interactions
Hair follicle
Sebaceous gland
url https://doi.org/10.1186/s13287-020-02104-9
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