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Inflammation-induced tissue damage mimicking GvHD in human skin models as test-platform for immunotherapeutics

: Wallstabe, Julia; Bussemer, Lydia; Groeber-Becker, Florian; Freund, Lukas; Alb, Miriam; Dragan, Mariola; Waaga-Gasser, Ana Maria; Jakubietz, Rafael; Kneitz, Hermann; Rosenwald, Andreas; Rebhan, Silke; Walles, Heike; Mielke, Stephan

Volltext ()

Alternatives to animal experimentation : ALTEX 37 (2020), Nr.3, S.429-440
ISSN: 1868-596X (Print)
ISSN: 0946-7785
ISSN: 1868-8551 (Online)
Zeitschriftenaufsatz, Elektronische Publikation
Fraunhofer ISC ()
alloreactivity; cytokine-release syndrome; graft-versus-host disease; Human tissue models; product testing

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.