Thomas Biedermann

Thomas Biedermann
University of Zurich | UZH · Tissue Biology Research Unit

PhD

About

81
Publications
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2,271
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Publications

Publications (81)
Article
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The basal layer of human interfollicular epidermis has been described to harbour both quiescent keratinocyte stem cells and a transit amplifying cell population that maintains the suprabasal epidermal layers. We performed immunofluorescence analyses and revealed that the main proliferative keratinocyte pool in vivo resides suprabasally. We isolated...
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The evidence for fibroblast heterogeneity is continuously increasing, and recent work has shed some light on the existence of different sub-populations of fibroblasts in the human skin. Although we now have a more precise understanding of their distribution in the human body, we do not know whether their properties are predictive of where these cel...
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Extensive availability of engineered autologous dermo-epidermal skin substitutes (DESS) with functional and structural properties of normal human skin represents a goal for the treatment of large skin defects such as severe burns. Recently, a clinical phase I trial with this type of DESS was successfully completed, which included patients own kerat...
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CD200 is a cell membrane glycoprotein that interacts with its structurally related receptor (CD200R) expressed on immune cells. We characterized CD200–CD200R interactions in human adult/juvenile (j/a) and fetal (f) skin and in in vivo prevascularized skin substitutes (vascDESS) prepared by co-culturing human dermal microvascular endothelial cells (...
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CD157 acts as a receptor, regulating leukocyte trafficking and the binding of extracellular matrix components. However, the expression pattern and the role of CD157 in human blood (BEC) and the lymphatic endothelial cells (LEC) of human dermal microvascular cells (HDMEC), remain elusive. We demonstrated constitutive expression of CD157 on BEC and L...
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It is still unknown whether the human interfollicular epidermis harbors a reservoir of melanocyte precursor cells. Here, we clearly distinguish between three distinct types of melanocytes in human interfollicular epidermis: (1) cKit⁺CD90–, (2) cKit⁺CD90⁺, and (3) cKit⁻CD90⁺. Importantly, we identify the Kit tyrosine kinase receptor (cKit) as a mark...
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CD26, also known as dipeptidyl peptidase IV (DPPIV), is a multifunctional transmembrane protein playing a significant role in the cutaneous wound healing processes in the mouse skin. However, only scarce data are available regarding the distribution and function of this protein in the human skin. Therefore, the aim of this study was to investigate...
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The immune system has a crucial role in skin wound healing and the application of specific cell-laden immunomodulating biomaterials emerged as a possible treatment option to drive skin tissue regeneration. Cell-laden tissue-engineered skin substitutes have the ability to activate immune pathways, even in the absence of other immune-stimulating sign...
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Severe injuries to skin including hypodermis require full-thickness skin replacement. Here, we bio-engineered a tri-layered human skin substitute (TLSS) containing the epidermis, dermis, and hypodermis. The hypodermal layer was generated by differentiation of human adipose stem cells (ASC) in a collagen type I hydrogel and combined with a prevascul...
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The clinical treatment of large, full-thickness skin injuries with tissue-engineered autologous dermo–epidermal skin substitutes is an emerging alternative to split-thickness skin grafting. However, their production requires about one month of in vitro cell and tissue culture, which is a significant drawback for the treatment of patients with sever...
Article
The cover image is based on the Original Article Bioengineering and in utero transplantation of fetal skin in the sheep model: A crucial step towards clinical application in human fetal spina bifida repair by Luca Mazzone, THOMAS BIEDERMANN, Ernst Reichmann et al., https://doi.org/10.1002/term.2963.
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Background: An intricate problem during open human fetal surgery for spina bifida regards back skin closure, particularly in those cases where the skin defect is much too large for primary closure. We hypothesize that tissue engineering of fetal skin might provide an adequate autologous skin substitute for in utero application in such situations....
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Purpose: Open fetal spina bifida repair has become a novel clinical standard of care. In very large spina bifida lesions, the skin defect cannot be covered primarily, asking for alternative solutions. We hypothesize that amniotic fluid stem cells (AFSC) could be differentiated into keratinocytes that could then be used to bioengineer autologous sk...
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Human autologous bioengineered skin has been successfully developed and used to treat skin injuries in a growing number of cases. In current clinical studies, the biomaterial used is fabricated via plastic compression of collagen hydrogel to increase the density and stability of the tissue. To further facilitate clinical adoption of bioengineered s...
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Aim of the study The use of autologous bio-engineered dermo-epidermal skin substitutes (DESS) yields a pivotal opportunity to cover large skin defects in human patients. These skin grafts consist of both epidermal and dermal compartments necessary for robust and permanent functional wound closure. In this study, we investigated the impact of mesenc...
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Purpose Ultraviolet (UV) radiation adversely affects skin health at cellular and molecular levels. Hence, UV radiation can directly induce inflammatory responses in the dermis by inducing erythema, edema, inflammation, dermal fibroblasts alterations, and extracellular matrix modifications. Methods Human keratinocytes, melanocytes, and fibroblasts...
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By forming a protective barrier, epidermal keratinocytes represent the first line of defense against environmental insults. UVB radiation of the sun is a major challenge for the skin and can induce inflammation, aging and eventually skin cancer. UVB induces an immune response in human keratinocytes resulting in activation and secretion of the pro-i...
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Aims and objectives: The use of autologous tissue-engineered skin substitutes is a promising approach to cover large skin defects in patients. Preclinical investigation is pivotal to test and improve the quality of these bio-engineered substitutes. In the skin, the epidermis, formed mainly by keratinocytes, provides the first physical barrier prot...
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Aims and objectivesVascularized bio-engineered human dermo-epidermal skin substitutes (vascDESS) hold promise for treating burn patients, including those with severe full-thickness wounds. We have previously shown that vascDESS promote wound healing by enhanced influx of macrophages and granulocytes. Immediately following transplantation, macrophag...
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Inflammasomes are multimeric protein complexes that assemble upon sensing of a variety of stress factors. Their formation results in caspase-1-mediated activation and secretion of the pro-inflammatory cytokines pro-interleukin(IL)-1β and -18, which induce an inflammatory response. Inflammation is supported by a lytic form of cell death, termed pyro...
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Statement of significance: Molecular and mechanical interactions with the surrounding environment are essential for cell functions. Although 2D culture systems greatly contributed to our understanding of complex biological phenomena, they cannot substitute for crucial interaction that take place in 3D. 3D culture systems aim to overcome limitation...
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The originally published version of this Article was updated shortly after publication to add the words 'The' and 'affinity' to the title, following their inadvertent removal during the production process. This has now been corrected in both the PDF and HTML versions of the Article.
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Cutaneous melanoma represents the most fatal skin cancer due to its high metastatic capacity. According to the “phenotype switching” model, the aggressive nature of melanoma cells results from their intrinsic potential to dynamically switch from a high-proliferative/low-invasive to a low-proliferative/high-invasive state. Here we identify the low a...
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We developed human dermo-epidermal skin substitutes which are presently applied in phase I and II clinical trials. Here we used these very same skin equivalents containing melanocytes, named MelSkin, as an experimental skin model. We investigated the effects of UVB irradiation on the skin grafts transplanted on immune-compromised rats. The irradiat...
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There is accumulating evidence that interactions between epidermal melanocytes and stromal cells play an important role in the regulation of skin pigmentation. In this study we established a pigmented dermo-epidermal skin model (melDESS) of human origin to investigate the effects of distinct stromal cells on melanogenesis. melDESS is a complex, cli...
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Purpose Autologous bio-engineered dermo-epidermal skin substitutes (DESS) represent an alternative therapeutic option for a definitive treatment of skin defects in human patients. Largely, the interaction of host immune cells with transplanted DESS is considered to be essential for the granulation tissue formation, graft take, and its functionality...
Article
Autologous bio-engineered dermo-epidermal skin substitutes are a promising treatment for large skin defects such as burns. For their successful clinical application, the graft dressing must protect and support the keratinocyte layer and, in many cases, possess antimicrobial properties. However, silver in many antimicrobial dressings may inhibit ker...
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Perception of the adipose tissue has changed dramatically over the last few decades. Identification of adipose-derived stem cells (ASCs) ultimately transformed paradigm of this tissue from a passive energy depot into a promising stem cell source with properties of self-renewal and multipotential differentiation. As compared to bone marrow-derived s...
Chapter
Dieses Kapitel beschäftigt sich mit der Herstellung, Untersuchung und klinischen Anwendung von künstlichen Ersatzstoffen für Haut sowie ex vivo erzeugter menschlicher Haut. Es erfolgt ein historischer Abriss der Entwicklung von Ersatzmaterialien und zellulärem Hautersatz für spezifische Schichten der Haut und gibt einen Überblick über ihre heutige...
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Burns and other severe skin injuries alter cutaneous perception of pain, temperature, and touch. During skin wound healing, peripheral nerve regeneration can occur from nerve endings of the wound bed, however, a functional recovery after an injury is often not sufficient due to scar formation or impaired wound healing.
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Purpose: The clinical application of autologous tissue-engineered skin analogs is an important strategy to cover large skin defects. Investigating biological dynamics, such as reinnervation after transplantation, is essential to improve the quality of such skin analogs. Previously, we have examined that our skin substitutes are reinnervated by hos...
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Purpose: The need for clinically applicable skin substitutes continues to be a matter of fact. Hypothetically, a laboratory grown autologous skin analog with near normal architecture might be a suitable approach to yield both satisfactory functional and cosmetic long-term results. In this study, we explored the use of human endothelial cells derive...
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PURPOSE Transplantation of pigmented tissue-engineered human autologous skin substitutes represents a promising procedure to cover skin defects. We have already demonstrated that we can restore the patient's native light or dark skin color by adding melanocytes to our dermo-epidermal skin analogs. In this long-term study, we investigated if melanoc...
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PURPOSE Human pigmented tissue-engineered skin substitutes represent an advanced therapeutic option to treat skin defects. The inflammatory response is one of the major factors determining integration and long-term survival of such a graft in vivo. The aim of the present study was to investigate the spatiotemporal distribution of host-derived macro...
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It has been shown in vitro that melanocyte proliferation and function in palmoplantar skin is regulated by mesenchymal factors derived from fibroblasts. Here, we investigated in vivo the influence of mesenchymal-epithelial interactions in human tissue-engineered skin substitutes reconstructed from palmar- and non-palmoplantar-derived fibroblasts. T...
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In our laboratory, we have been using human pigmented dermo-epidermal skin substitutes for short term experiments since several years. Little is known, however, about the long-term biology of such constructs after transplantation. We constructed human, melanocyte-containing dermo-epidermal skin substitutes of different (light and dark) pigmentation...
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http://www.karger.com/Article/Pdf/362490 Background: Congenital melanocytic nevi (CMNs) are melanocytic neoplasms that can transform into melanoma. However, this development is impeded in the majority of cases and mostly affects patients with large or giant CMNs. Methods: To elucidate mechanisms that keep CMNs from malignant transformation, CMN tis...
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In our previous work we showed that human sweat gland-derived epithelial cells represent an alternative source of keratinocytes to grow a near normal autologous epidermis. The role of subtypes of sweat gland cells in epidermal regeneration and maintenance remained unclear. In this study, we compare the regenerative potential of both, secretory and...
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Background: Congenital melanocytic nevi (CMNs) are melanocytic neoplasms that can transform into melanoma. However, this development is impeded in the majority of cases and mostly affects patients with large or giant CMNs. Methods: To elucidate mechanisms that keep CMNs from malignant transformation, CMN tissue biopsies were investigated for p-ERK...
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Bioengineered dermo-epidermal skin analogs containing melanocytes represent a promising approach to cover large skin defects including restoration of the patient's own skin color. So far, little is known about the development of blood and lymphatic vessels in pigmented skin analogs after transplantation. In this experimental study, we analyzed the...
Article
Human autologous tissue-engineered skin grafts are a promising way to cover skin defects. Clearly, it is mandatory to study essential biological dynamics after transplantation, including reinnervation. Previously, we have already shown that human tissue-engineered skin analogs are reinnervated by host nerve fibers as early as 8 weeks after transpla...
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It is unclear whether dermal fibroblasts are indispensable key players for tissue engineering of dermo-epidermal skin analogs. In this experimental study, we wanted to test the hypothesis that tonsil-derived mesenchymal cells can assume the role of dermal fibroblasts when culturing pigmented skin analogs for transplantation. Mesenchymal cells from...
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Over the past few decades, important milestones have been reached in the field of skin tissue engineering, bringing the ultimate goal of fabricating an autologous dermoepidermal skin substitute with all its cellular components and skin appendages closer to reality. Yet, scientific progress alone is not enough, clinical demands must be addressed and...
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We have previously reported a model for melanoma progression in which oscillation between melanoma cell phenotypes characterized by invasion or proliferation is fundamental to tumor heterogeneity and disease progression ADDIN EN.CITE ADDIN EN.CITE.DATA (Hoek et al., 2006). In this study we examine the possible role of hypoxia as one of the microenv...
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Introduction: Autologous dermo-epidermal skin substitutes (DESS) generated in vitro represent a promising therapeutic means to treat full-thickness skin defects in clinical practice. A serious drawback with regard to acute patients is the relatively long production time of 3-4 weeks. With this experimental study we aimed to decrease the production...
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Background: Currently, acellular dermal substitutes used for skin reconstruction are usually covered with split-thickness skin grafts. The goal of this study was to develop an animal model in which such dermal substitutes can be tested under standardized conditions using a bioengineered dermo-epidermal skin graft for coverage. Methods: Bioengine...
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Extensive full-thickness skin loss, associated with deep burns or other traumata, represents a major clinical problem that is far from being solved. A promising approach to treat large skin defects is the use of tissue-engineered full-thickness skin analogues with nearly normal anatomy and function. In addition to excellent biological properties, s...
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Purpose: Autologous skin substitutes to cover large skin defects are used since several years. Melanocytes, although essential for solar protection and pigmentation of skin, are not yet systematically added to such substitutes. In this experimental study, we reconstructed melanocyte-containing dermo-epidermal skin substitutes from donor skins of d...
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Purpose: Tissue engineered skin substitutes are a promising tool to cover large skin defects, but little is known about reinnervation of transplants. In this experimental study, we analyzed the ingrowth of host peripheral nerve fibers into human tissue engineered dermo-epidermal skin substitutes in a rat model. Using varying cell types in the epid...
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Purpose: Human amniotic fluid comprises cells with high differentiation capacity, thus representing a potential cell source for skin tissue engineering. In this experimental study, we investigated the ability of human amniotic fluid derived cells to substitute dermal fibroblasts and support epidermis formation and stratification in a humanized ani...
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Recently, Biedermann et al. (2010) have demonstrated that human eccrine sweat gland cells can develop a multilayered epidermis. The question still remains whether these cells can fulfill exclusive and very specific functional properties of epidermal keratinocytes, such as the incorporation of melanin, a feature absent in sweat gland cells. We added...
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Tissue engineering of clinically applicable dermo-epidermal skin substitutes is crucially dependent on the three-dimensional extracellular matrix, supporting the biological function of epidermal and dermal cells. This matrix essentially determines the mechanical stability of these substitutes to allow for safe and convenient surgical handling. Coll...
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Dermal templates, such as Matriderm® and Integra®, are widely used in plastic and reconstructive surgery, often as two-step procedures. A recent development is the application of thin dermal templates covered with split thickness skin grafts in one-step procedures. In this experimental study, we compare the two thin matrices Matriderm® 1 mm and Int...
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To overcome the lack of effective therapeutics for aggressive melanoma, new research models closely resembling the human disease are required. Here we report the development of a fully orthotopic, humanized in vivo model for melanoma, faithfully recapitulating human disease initiation and progression. To this end, human melanoma cells were seeded i...
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Self-filling, hydrogel-based osmotic tissue expanders have been successfully used for several years, mainly in adult patients. We wanted to test this novel device in pediatric plastic and reconstructive surgery. Between November 2004 and September 2009, we implanted 53 osmotic tissue expanders following standard surgical principles in a total of 30...