TY  - JOUR
A1  - Groeber, Florian
A1  - Engelhardt, Lisa
A1  - Lange, Julia
A1  - Kurdyn, Szymon
A1  - Schmid, Freia F.
A1  - Rücker, Christoph
A1  - Mielke, Stephan
A1  - Walles, Heike
A1  - Hansmann, Jan
T1  - A First Vascularized Skin Equivalent as an Alternative to Animal Experimentation
JF  - ALTEX - Alternatives to Animal Experimentation
N2  - Tissue-engineered skin equivalents mimic key aspects of the human skin, and can thus be employed as wound coverage for large skin defects or as in vitro test systems as an alternative to animal models. However, current skin equivalents lack a functional vasculature limiting clinical and research applications. This study demonstrates the generation of a vascularized skin equivalent with a perfused vascular network by combining a biological vascularized scaffold (BioVaSc) based on a decellularized segment of a porcine jejunum and a tailored bioreactor system. Briefly, the BioVaSc was seeded with human fibroblasts, keratinocytes, and human microvascular endothelial cells. After 14 days at the air-liquid interface, hematoxylin & eosin and immunohistological staining revealed a specific histological architecture representative of the human dermis and epidermis including a papillary-like architecture at the dermal-epidermal-junction. The formation of the skin barrier was measured non-destructively using impedance spectroscopy. Additionally, endothelial cells lined the walls of the formed vessels that could be perfused with a physiological volume flow. Due to the presence of a complex in-vivo-like vasculature, the here shown skin equivalent has the potential for skin grafting and represents a sophisticated in vitro model for dermatological research.
KW  - alternative to animal testing
KW  - skin equivalents
KW  - tissue engineering
KW  - vascularization
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164438
VL  - 33
IS  - 4
ER  - 
TY  - JOUR
A1  - Wallstabe, Julia
A1  - Bussemer, Lydia
A1  - Groeber-Becker, Florian
A1  - Freund, Lukas
A1  - Alb, Mirian
A1  - Dragan, Mariola
A1  - Waaga-Gasser, Ana Maria
A1  - Jakubietz, Rafael
A1  - Kneitz, Hermann
A1  - Rosenwald, Andreas
A1  - Rebhan, Silke
A1  - Walles, Heike
A1  - Mielke, Stephan
T1  - Inflammation-Induced Tissue Damage Mimicking GvHD in Human Skin Models as Test Platform for Immunotherapeutics
JF  - ALTEX
N2  - Due to the rapidly increasing development and use of cellular products, there is a rising demand for non-animal-based test platforms to predict, study and treat undesired immunity. Here, we generated human organotypic skin models from human biopsies by isolating and expanding keratinocytes, fibroblasts and microvascular endothelial cells and seeding these components on a collagen matrix or a biological vascularized scaffold matrix in a bioreactor. We then were able to induce inflammation-mediated tissue damage by adding pre-stimulated, mismatched allogeneic lymphocytes and/or inflammatory cytokine-containing supernatants histomorphologically mimicking severe graft versus host disease (GvHD) of the skin. This could be prevented by the addition of immunosuppressants to the models. Consequently, these models harbor a promising potential to serve as a test platform for the prediction, prevention and treatment of GvHD. They also allow functional studies of immune effectors and suppressors including but not limited to allodepleted lymphocytes, gamma-delta T cells, regulatory T cells and mesenchymal stromal cells, which would otherwise be limited to animal models. Thus, the current test platform, developed with the limitation that no professional antigen presenting cells are in place, could greatly reduce animal testing for investigation of novel immune therapies.
KW  - inflammation-induced tissue demage
KW  - immunotherapeutics
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229974
VL  - 37
IS  - 3
ER  -