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Mechanical tension stimulates the transdifferentiation of fibroblasts into myofibroblasts in human burn scars
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden.
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
2008 (English)In: Burns : journal of the International Society for Burn Injuries, ISSN 1879-1409, Vol. 34, no 7, 942-6 p.Article in journal (Refereed) Published
Abstract [en]

Scar formation as a result of burn wounds leads to contraction of the formed granulation tissue, which causes both aesthetic and functional impairment for the patient. Currently, the main treatment methods focus on stretching to prevent tissue contraction. The myofibroblasts play a key role in the contraction of granulation tissue during scar formation, but their presence should normally decrease after wound re-epithelialization. In hypertrophic scars the myofibroblasts persist and is believed to cause further hypertrophy. Previous studies have shown that mechanical tension leads to increased myofibroblast numbers in granulation tissue. In order to evaluate the effect mechanical tension as a result of stretching has on the number of myofibroblasts in burn wound scars, an in vitro model was used. This model used human burn scar biopsies which were stretched and examined after 1 and 6 days to evaluate the effect on the number of myofibroblasts. The stretching caused an increase in the number of myofibroblasts after mechanical stimulation. This indicates that mechanical stimulation using stretching induces fibroblast to myofibroblast transdifferentiation, thus underlining the importance of further investigations of optimal methods of this regime for treating burn scars.

Place, publisher, year, edition, pages
2008. Vol. 34, no 7, 942-6 p.
Keyword [en]
Burns, Myofibroblast, Fibroblast, Transdifferentiation, Stretching
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-19712DOI: 10.1016/j.burns.2008.01.010PubMedID: 18472340OAI: oai:DiVA.org:liu-19712DiVA: diva2:227682
Available from: 2009-07-16 Created: 2009-07-16 Last updated: 2009-08-12Bibliographically approved
In thesis
1. Human Dermal Fibroblasts in Tissue Engineering
Open this publication in new window or tab >>Human Dermal Fibroblasts in Tissue Engineering
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The loss or failure of tissues and/or organs is one of the most frequent problems in modern healthcare. The field of tissue engineering applies the principles of biology and engineering in order to develop functional substitutes for damaged tissues. Tissue engineering contains elements of medicine, material science and engineering with major components in focus being cells, biomaterials and soluble factors. All three components may be required for the development of clinical treatments.

The usage of autologous tissue specific cells for clinical treatment is often not feasible due to poor growth kinetics or unstable phenotypes of the cells. Furthermore, lack of availability of healthy tissue that can be biopsied is a major problem in many applications. One approach to overcome this problem is to use adult stem cells which have the capacity to give rise to several different cell types. Although promising, adult stem cells have major impediments for use in several tissue engineering applications. The difficulties associated with harvest, culture and storage render problems in the development of clinically relevant procedures.

During the last years, the inherent plasticity of differentiated somatic cells has been demonstrated. One of the easiest human cell types to obtain, expand and store is the dermal fibroblast. Recent reports indicate that dermal fibroblasts can be induced to differentiate towards several distinct mesenchymal lineages in vitro.

The main aim of this thesis was to investigate the inherent stem cell plasticity of human dermal fibroblasts and explore their possible usefulness in tissue engineering applications. The papers included in this thesis employ routine and immunohistochemical staining, enzyme activity assay, analysis of low density lipoprotein incorporation, capillary-like network formation assay and full expression micro array analysis.

Fibroblasts were shown to differentiate towards adipocyte, chondrocyte, endothelial and osteoblast-like cell types in vitro. The differentiation from fibroblasts to myofibroblasts in burn scar tissue upon stimulation by mechanical tension was also demonstrated. Adipogenic, chondrogenic and osteogenic induced fibroblasts display the upregulation of several genes associated with adipocytes, chondrocytes and osteoblasts.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2009. 56 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1133
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-19716 (URN)978-91-7393-618-7 (ISBN)
Public defence
2009-08-27, Berzeliussalen, Campus US, Linköpings Universitet, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2009-07-16 Created: 2009-07-16 Last updated: 2009-09-15Bibliographically approved

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Junker, Johan P EKratz, Gunnar

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