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Human melanocytes mitigate keratinocyte-dependent contraction in an in vitro collagen contraction assay
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
2015 (English)In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 41, no 5, 1035-1042 p.Article in journal (Refereed) Published
Abstract [en]

Scarring is an extensive problem in burn care, and treatment can be especially complicated in cases of hypertrophic scarring. Contraction is an important factor in scarring but the contribution of different cell types remains unclear. We have investigated the contractile behavior of keratinocytes, melanocytes and fibroblasts by using an in vitro collagen gel assay aimed at identifying a modulating role of melanocytes in keratinocyte-mediated contraction. Cells were seeded on a collagen type I gel substrate and the change in gel dimensions were measured over time. Hematoxylin and Eosin-staining and immunohistochemistry against pan-cytokeratin and microphthalmia-associated transcription factor showed that melanocytes integrated between keratinocytes and remained there throughout the experiments. Keratinocyte- and fibroblast-seeded gels contracted significantly over time, whereas melanocyte-seeded gels did not. Co-culture assays showed that melanocytes mitigate the keratinocyte-dependent contraction (significantly slower and 18-32% less). Fibroblasts augmented the contraction in most assays (approximately 6% more). Non-contact co-cultures showed some influence on the keratinocyte-dependent contraction. Results show that mechanisms attributable to melanocytes, but not fibroblasts, can mitigate keratinocyte contractile behavior. Contact-dependent mechanisms are stronger modulators than non-contact dependent mechanisms, but both modes carry significance to the contraction modulation of keratinocytes. Further investigations are required to determine the mechanisms involved and to determine the utility of melanocytes beyond hypopigmentation in improved clinical regimes of burn wounds and wound healing.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD , 2015. Vol. 41, no 5, 1035-1042 p.
Keyword [en]
Melanocytes; Keratinocytes; Contraction; Wound healing; Fibroblasts; Scars
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-120329DOI: 10.1016/j.burns.2014.10.034ISI: 000357350100015PubMedID: 25466959OAI: oai:DiVA.org:liu-120329DiVA: diva2:843914
Available from: 2015-07-31 Created: 2015-07-31 Last updated: 2016-03-09
In thesis
1. Fibroblast Differentiation and Models of Human Skin
Open this publication in new window or tab >>Fibroblast Differentiation and Models of Human Skin
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis combines three publications and one manuscript, covering two principal topics: functional differentiation of human fibroblasts and laboratory models of human skin. The two topics favourably unite in the realm of tissue engineering. This thesis is therefore split into three main parts: 1. a discussion of phenotypic plasticity as it pertains to fibroblasts and the stem cell continuum; 2. a short review of engineered tissue, with particular focus on soluble factors and materials; and, 3. a motivated review of the biology, diversity and culture of skin, including skin construction.

The intended goal of our research endeavor was to achieve the  formulation of a bioactive therapy for skin regeneration. The main hypothesis was that fibroblast-to-keratinocyte differentiation would facilitate wound healing, and that the protocol for such a method could be adapted to clinical translation. The foundation for the hypothesis lay in the differentiation capabilities of primary dermal fibroblasts (Paper I). However, the goal has not yet been achieved. Instead, intermediate work on the construction of skin for the purpose of creating a model test-bed has resulted in two other publications. The use of excised human skin, a formidable reference sample for tissue engineered skin, has been used to investigate a gelatinbased material in re-epithelialization (Paper II). A first attempt at standardizing a constructed skin model also resulted in a publication: an evaluation of melanocyte influences on keratinocyte-mediated contraction (Paper III).

The introduction of melanocytes into a skin model raised questions about other appendages of the integumentary system. Our previous experience with preadipocyte isolation and identification, and our attempts at constructing three-dimensional adipose tissue, motivated further investigations into fibroblast-to-adipocyte differentiation. We investigated the possibility of activating thermogenesis in fibroblasts, a property otherwise reserved for cells of the adipogenic and myogenic lineages. Our attempts were successful, and are presently in manuscript form (Paper IV). Some further experiments and optimizations are necessary before establishing a reproducible protocol for thermogenic induction.

The knowledge obtained through these scientific inquiries have moved us closer to achieving our goals, but methodological advances are still necessary. In the meantime, we have new test-beds for investigating different interactions in skin, and that enables many new questions to be asked and answered.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. 188 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1506
National Category
Cell Biology Medical Biotechnology
Identifiers
urn:nbn:se:liu:diva-125925 (URN)10.3384/diss.diva-125925 (DOI)978-91-7685-849-3 (Print) (ISBN)
Public defence
2016-04-08, Hasselquistsalen, ingång 76 pl 9, Campus US, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2016-03-09 Created: 2016-03-09 Last updated: 2016-04-12Bibliographically approved

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