Human fetal skin derived merkel cells display distinctive characteristics in vitro and in bio-engineered skin substitutes in vivo

Human skin contains specialized neuroendocrine Merkel cells responsible for fine touch sensation. In the present study, we performed in-depth analysis of Merkel cells in human fetal back skin. We revealed that these Merkel cells expressed cytokeratin 20 (CK20), were positive for the neuroendocrine m...

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Main Authors: Katarzyna Michalak-Micka, Dominic Rütsche, Luca Mazzone, Vanessa L. Büchler, Ueli Moehrlen, Agnes S. Klar, Thomas Biedermann
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-09-01
Series:Frontiers in Bioengineering and Biotechnology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fbioe.2022.983870/full
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author Katarzyna Michalak-Micka
Katarzyna Michalak-Micka
Dominic Rütsche
Dominic Rütsche
Luca Mazzone
Luca Mazzone
Luca Mazzone
Vanessa L. Büchler
Vanessa L. Büchler
Ueli Moehrlen
Ueli Moehrlen
Ueli Moehrlen
Ueli Moehrlen
Agnes S. Klar
Agnes S. Klar
Thomas Biedermann
Thomas Biedermann
Thomas Biedermann
author_facet Katarzyna Michalak-Micka
Katarzyna Michalak-Micka
Dominic Rütsche
Dominic Rütsche
Luca Mazzone
Luca Mazzone
Luca Mazzone
Vanessa L. Büchler
Vanessa L. Büchler
Ueli Moehrlen
Ueli Moehrlen
Ueli Moehrlen
Ueli Moehrlen
Agnes S. Klar
Agnes S. Klar
Thomas Biedermann
Thomas Biedermann
Thomas Biedermann
author_sort Katarzyna Michalak-Micka
collection DOAJ
description Human skin contains specialized neuroendocrine Merkel cells responsible for fine touch sensation. In the present study, we performed in-depth analysis of Merkel cells in human fetal back skin. We revealed that these Merkel cells expressed cytokeratin 20 (CK20), were positive for the neuroendocrine markers synaptophysin and chromogranin A, and the mechanosensitive ion channel Piezo2. Further, we demonstrated that Merkel cells were present in freshly isolated human fetal epidermal cells in vitro, and in tissue-engineered human dermo-epidermal skin substitutes 4 weeks after transplantation on immune-compromised rats. Merkel cells retained the expression of CK20, synaptophysin, chromogranin A, and Piezo2 after isolation and in culture, and in the skin substitutes after transplantation. Interestingly, we observed that in fetal skin and in skin substitutes, only Merkel cells were positive for CK8, while in culture, also non-Merkel cells showed positivity for CK8. In summary, human fetal Merkel cells showed phenotypical features confirming their cell identity. This findings are of pivotal importance for the future application of fetal tissue-engineered skin in clinics.
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spelling doaj.art-60bf9fb1a7994e4a9e025c38298941bb2022-12-22T04:04:22ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-09-011010.3389/fbioe.2022.983870983870Human fetal skin derived merkel cells display distinctive characteristics in vitro and in bio-engineered skin substitutes in vivoKatarzyna Michalak-Micka0Katarzyna Michalak-Micka1Dominic Rütsche2Dominic Rütsche3Luca Mazzone4Luca Mazzone5Luca Mazzone6Vanessa L. Büchler7Vanessa L. Büchler8Ueli Moehrlen9Ueli Moehrlen10Ueli Moehrlen11Ueli Moehrlen12Agnes S. Klar13Agnes S. Klar14Thomas Biedermann15Thomas Biedermann16Thomas Biedermann17Tissue Biology Research Unit, Department of Surgery, University Children’s Hospital Zurich, Zurich, SwitzerlandChildren’s Research Center (CRC), University Children’s Hospital Zurich, Zurich, SwitzerlandTissue Biology Research Unit, Department of Surgery, University Children’s Hospital Zurich, Zurich, SwitzerlandChildren’s Research Center (CRC), University Children’s Hospital Zurich, Zurich, SwitzerlandChildren’s Research Center (CRC), University Children’s Hospital Zurich, Zurich, SwitzerlandSpina Bifida Center, University Children’s Hospital Zurich, Zurich, SwitzerlandThe Zurich Center for Fetal Diagnosis and Therapy, University of Zurich, Zurich, SwitzerlandTissue Biology Research Unit, Department of Surgery, University Children’s Hospital Zurich, Zurich, SwitzerlandChildren’s Research Center (CRC), University Children’s Hospital Zurich, Zurich, SwitzerlandChildren’s Research Center (CRC), University Children’s Hospital Zurich, Zurich, SwitzerlandSpina Bifida Center, University Children’s Hospital Zurich, Zurich, SwitzerlandThe Zurich Center for Fetal Diagnosis and Therapy, University of Zurich, Zurich, SwitzerlandFaculty of Medicine, University of Zurich, Zurich, SwitzerlandTissue Biology Research Unit, Department of Surgery, University Children’s Hospital Zurich, Zurich, SwitzerlandChildren’s Research Center (CRC), University Children’s Hospital Zurich, Zurich, SwitzerlandTissue Biology Research Unit, Department of Surgery, University Children’s Hospital Zurich, Zurich, SwitzerlandChildren’s Research Center (CRC), University Children’s Hospital Zurich, Zurich, SwitzerlandFaculty of Medicine, University of Zurich, Zurich, SwitzerlandHuman skin contains specialized neuroendocrine Merkel cells responsible for fine touch sensation. In the present study, we performed in-depth analysis of Merkel cells in human fetal back skin. We revealed that these Merkel cells expressed cytokeratin 20 (CK20), were positive for the neuroendocrine markers synaptophysin and chromogranin A, and the mechanosensitive ion channel Piezo2. Further, we demonstrated that Merkel cells were present in freshly isolated human fetal epidermal cells in vitro, and in tissue-engineered human dermo-epidermal skin substitutes 4 weeks after transplantation on immune-compromised rats. Merkel cells retained the expression of CK20, synaptophysin, chromogranin A, and Piezo2 after isolation and in culture, and in the skin substitutes after transplantation. Interestingly, we observed that in fetal skin and in skin substitutes, only Merkel cells were positive for CK8, while in culture, also non-Merkel cells showed positivity for CK8. In summary, human fetal Merkel cells showed phenotypical features confirming their cell identity. This findings are of pivotal importance for the future application of fetal tissue-engineered skin in clinics.https://www.frontiersin.org/articles/10.3389/fbioe.2022.983870/fullhuman fetal skinMerkel cellCK20skin substituteskin tissue engineering
spellingShingle Katarzyna Michalak-Micka
Katarzyna Michalak-Micka
Dominic Rütsche
Dominic Rütsche
Luca Mazzone
Luca Mazzone
Luca Mazzone
Vanessa L. Büchler
Vanessa L. Büchler
Ueli Moehrlen
Ueli Moehrlen
Ueli Moehrlen
Ueli Moehrlen
Agnes S. Klar
Agnes S. Klar
Thomas Biedermann
Thomas Biedermann
Thomas Biedermann
Human fetal skin derived merkel cells display distinctive characteristics in vitro and in bio-engineered skin substitutes in vivo
Frontiers in Bioengineering and Biotechnology
human fetal skin
Merkel cell
CK20
skin substitute
skin tissue engineering
title Human fetal skin derived merkel cells display distinctive characteristics in vitro and in bio-engineered skin substitutes in vivo
title_full Human fetal skin derived merkel cells display distinctive characteristics in vitro and in bio-engineered skin substitutes in vivo
title_fullStr Human fetal skin derived merkel cells display distinctive characteristics in vitro and in bio-engineered skin substitutes in vivo
title_full_unstemmed Human fetal skin derived merkel cells display distinctive characteristics in vitro and in bio-engineered skin substitutes in vivo
title_short Human fetal skin derived merkel cells display distinctive characteristics in vitro and in bio-engineered skin substitutes in vivo
title_sort human fetal skin derived merkel cells display distinctive characteristics in vitro and in bio engineered skin substitutes in vivo
topic human fetal skin
Merkel cell
CK20
skin substitute
skin tissue engineering
url https://www.frontiersin.org/articles/10.3389/fbioe.2022.983870/full
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