Sub-populations of dermal skin fibroblasts secrete distinct extracellular matrix: implications for using skin substitutes in the clinic
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background
While several commercial dermoepidermal scaffolds can promote wound healing of the skin, the achievement of complete skin regeneration still represents a major challenge.
Objectives
To perform biological characterization of self‐assembled extracellular matrices (ECMs) from three different subpopulations of fibroblasts found in human skin: papillary fibroblasts (Pfi), reticular fibroblasts (Rfi) and dermal papilla fibroblasts (DPfi).
Methods
Fibroblast subpopulations were cultured with ascorbic acid to promote cell‐assembled matrix production for 10 days. Subsequently, cells were removed and the remaining matrices characterized. Additionally, in another experiment, keratinocytes were seeded on the top of cell‐depleted ECMs to generate epidermal‐only skin constructs.
Results
We found that the ECM self‐assembled by Pfi exhibited randomly oriented fibres associated with the highest interfibrillar space, reflecting ECM characteristics that are physiologically present within the papillary dermis. Mass spectrometry followed by validation with immunofluorescence analysis showed that thrombospondin 1 is preferentially expressed within the DPfi‐derived matrix. Moreover, we observed that epidermal constructs grown on DPfi or Pfi matrices exhibited normal basement membrane formation, whereas Rfi matrices were unable to support membrane formation.
Conclusions
We argue that inspiration can be taken from these different ECMs, to improve the design of therapeutic biomaterials in skin engineering applications.
While several commercial dermoepidermal scaffolds can promote wound healing of the skin, the achievement of complete skin regeneration still represents a major challenge.
Objectives
To perform biological characterization of self‐assembled extracellular matrices (ECMs) from three different subpopulations of fibroblasts found in human skin: papillary fibroblasts (Pfi), reticular fibroblasts (Rfi) and dermal papilla fibroblasts (DPfi).
Methods
Fibroblast subpopulations were cultured with ascorbic acid to promote cell‐assembled matrix production for 10 days. Subsequently, cells were removed and the remaining matrices characterized. Additionally, in another experiment, keratinocytes were seeded on the top of cell‐depleted ECMs to generate epidermal‐only skin constructs.
Results
We found that the ECM self‐assembled by Pfi exhibited randomly oriented fibres associated with the highest interfibrillar space, reflecting ECM characteristics that are physiologically present within the papillary dermis. Mass spectrometry followed by validation with immunofluorescence analysis showed that thrombospondin 1 is preferentially expressed within the DPfi‐derived matrix. Moreover, we observed that epidermal constructs grown on DPfi or Pfi matrices exhibited normal basement membrane formation, whereas Rfi matrices were unable to support membrane formation.
Conclusions
We argue that inspiration can be taken from these different ECMs, to improve the design of therapeutic biomaterials in skin engineering applications.
Date Issued
2018-08-01
Date Acceptance
2017-12-15
Citation
British Journal of Dermatology, 2018, 179 (2), pp.381-393
ISSN
1365-2133
Publisher
Wiley
Start Page
381
End Page
393
Journal / Book Title
British Journal of Dermatology
Volume
179
Issue
2
Copyright Statement
© 2017 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.
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.
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.
Sponsor
Medical Research Council (MRC)
Grant Number
MR/M01858X/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Dermatology
TISSUE-ENGINEERED SKIN
IN-VITRO
RETICULAR FIBROBLASTS
HAIR-FOLLICLES
STROMAL CELLS
REGENERATION
PAPILLARY
HETEROGENEITY
PROLIFERATION
EXPRESSION
1103 Clinical Sciences
1112 Oncology And Carcinogenesis
Dermatology & Venereal Diseases
Publication Status
Published
Date Publish Online
2017-12-20