ALTEX. 2020 Apr 14. doi: 10.14573/altex.1907181. [Epub ahead of print]

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

Wallstabe J¹, Bussemer L¹, Groeber-Becker F^2,3, Freund L¹, Alb M¹, Dragan M⁴, Waaga-Gasser AM⁴, Jakubietz R⁵, Kneitz H⁶, Rosenwald A⁷, Rebhan S¹, Walles H^2,3, Mielke S^8,1.

Abstract

With cellular products being on the front run 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 isolating and expanding keratinocytes, fibroblasts and microvascular endothelial cells finally allowing to seed these components on a collagen matrix or a biological vascularized scaffold matrix in a bioreactor. Afterwards, we were able to induce inflammation-based tissue damage by pre-stimulated mismatched allogeneic lymphocytes and/or inflammatory cytokine containing supernatants histomorphologically mimicking severe graft versus host disease (GvHD) of the skin. The effects could be prevented by the addition of immunosuppressants to the models. Consequently, these models would harbor a promising potential to serve as a test platform for the prediction, prevention and treatment of GvHD. This would 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 given that no professional APC are in place could highly reduce animal testing for investigation of novel immune therapies.