Due to the rapid increase in the development and use of cellular products, there is a growing demand for human testing platforms to predict, study, and treat unwanted immunity. Here, to produce organotypic human skin models, keratinocytes, fibroblasts, and microvascular endothelial cells were isolated from biopsies and seeded onto a collagen matrix or a biological vascularized scaffold matrix in a bioreactor. The addition of prestimulated mismatched allogeneic lymphocytes and/or proinflammatory cytokine-containing supernatants induced inflammation-mediated tissue injury that histomorphologically mimicked severe graft-versus-host disease (GvHD) of the skin. This was prevented by the addition of immunosuppressants to the models. Consequently, these models have promising potential to serve as a testing 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.
Inflammation-induced tissue damage mimicking GvHD in human skin models as test platform for immunotherapeutics
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